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PubMed2004

Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice.

Leptin can regulate several immune functions. However, the role of leptin on lymphocyte function has not been recognized in vivo. Accordingly, we have investigated the effect of leptin on starvation-induced immune dysfunction using diet-induced obese mice. To induce obesity, C57BL/6J mice were fed a high-fat diet for 14 weeks and control mice were fed a standard diet for the same period. The obese and control groups of mice were then starved for 48 h, and received intraperitoneal injections of recombinant leptin or phosphate-buffered saline four times during starvation. Other control mice in both diet groups were free fed without being starved. Although starvation of the control mice dramatically reduced the weights of the immune organs, cytokine production and increased proliferation of cultured splenocytes, these levels returned to those of the free-feeding groups with exogenous leptin administration. However, these effects of leptin were not observed in obese mice. These findings provide some evidence that leptin can regulate the immune function in vivo. It is also suggested that the action of leptin might not appear in obesity.

Animals↗
PubMed1994

Lymphokine production by human T cells in disease states.

A large body of evidence suggests the existence of polarized human T cell responses, reminiscent of Th1 and Th2 subsets described for mouse T cells. Human Th1-like cells preferentially develop during infections by intracellular bacteria, protozoa, and viruses, whereas Th2-like cells predominate during helminthic infestations and in response to common environmental allergens. The cytokine profile of "natural immunity" evoked by different offending agents in the context of different host genetic backgrounds appears to be a critical factor in determining the phenotype of the subsequent specific response. Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, they can also promote different immunopathological reactions. Th1-type responses appear to be involved in organ specific autoimmunity, in contact dermatitis, and in some chronic inflammatory disorders of unknown etiology. In contrast, in genetically predisposed hosts, Th2-type responses against common environmental allergens are responsible for triggering of allergic atopic disorders. Altered profiles of lymphokine production may account for immune dysfunctions in some primary or acquired immunodeficiency syndromes. The role of lymphokines produced by T cells in the pathogenesis of systemic autoimmune disorders is less clear. Further work is also required to better clarify the role of T cell-derived lymphokines in protecting against tumors or in favoring their development.

Autoimmune Diseases↗
PubMed2005

[The prognostic value of cellular immunity function in patients with hepatocellular carcinoma].

OBJECTIVES: To study the changes of cellular immunity function in patients with hepatocellular carcinoma (HCC) and its correlation with disease severity. METHODS: T lymphocyte subsets and CD28 co-stimulation molecule in CD8+ T cells in 22 HCC patients were detected using three-color flow cytometry. Serum interleukin-2 (IL-2), transforming growth factor beta 1 (TGFbeta1), and interleukin-6 (IL-6) were determined by ELISA and radioimmunoassay. A group of 30 patients with chronic hepatitis B (CHB), liver cirrhosis (LC), or normal adults (NC) served as controls. RESULTS: Compared with NC, the number of CD8+CD28- T cells increased and CD8+CD28+ T cells decreased in patients with HCC. The number of CD4+ T cells, CD4+/CD8+ ratios, IL-2 level all decreased and CD8+ T cells, IL-6, TGFbeta1 levels all increased in patients with HCC, LC and CHB. The CD4+ T cells, CD4+/CD8+ ratios and IL-2 level in patients with HCC were lower than those with CHB. Serum IL-6 and TGFbeta1 in patients with HCC were higher than those with LC and CHB. The levels of IL-6 and TGFbeta1 correlated with the stages of the tumors. CONCLUSIONS: HCC patients have a cellular immunity dysfunction. Rectifying the imbalanced function could be a potential way for treating HCC. Measurement of these factors would be useful for early diagnosis and evaluating the prognoses of these patients.

Adult↗
PubMed1994

A test of the immunoreactive theory for the origin of neurodevelopmental disorders in the offspring of women with immune disorder.

Gualtieri and Hicks (1985) proposed that male vulnerability for neurodevelopmental disorders (NDs) was partially due to intrauterine immune attack of the fetus. One group of mothers with heightened immunoreactivity might be women with immune disorder. This was tested within an epidemiological sample of 17,283 mother/child pairs. Maternal immune disorders considered were ulcerative colitis or asthma. NDs in the child included: cerebral palsy, mental retardation, seizures, articulation disorder, reading, or arithmetic disability, verbal or performance aptitude deficits, and attention deficit disorder. Unlike prior studies, we controlled for demographic perinatal variables that might confound interpretation of the data. Results indicated that immune dysfunction in the mother, be it autoimmune (ulcerative colitis) or defensive (asthma) was not associated with an increased incidence of any NDs in the offspring, but mothers with ulcerative colitis did have a disproportionate number of offspring who were non-right handed. Few variables discriminated between the children of ulcerative colitis mothers who became right handed when compared to those who did not. We suggest that a) only certain maternal autoimmune disorders such as systemic lupus erythematosus (but not ulcerative colitis or asthma) elevate the risk of intrauterine immune attack and b) the elevated rate of non-right handed offspring among ulcerative colitis mothers was not an instance of immune attack but instead represents some kind of genetic association.

Achievement↗
PubMed2026

A cuproptosis-related lncRNAs-based risk signature for predicting prognosis and immune status in glioma.

BACKGROUND: Glioma is one of the most prevalent primary malignant brain tumors, characterized by poor prognosis and limited treatment options. Recent studies have identified cuproptosis, a novel copper-dependent form of regulated cell death, as a critical mechanism involved in tumor progression. However, the role of cuproptosis-related long non-coding RNAs (lncRNAs) in glioma remains not fully clarified. This study aimed to develop and validate a prognostic model based on cuproptosis-associated lncRNAs to predict patient outcomes and guide individualizing therapeutic strategies. METHODS: Transcriptomic profiles and clinical data were obtained from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and the Chinese Glioma Genome Atlas (CGGA) databases. Cuproptosis -related prognostic lncRNAs were filtered via univariate and multivariate Cox and Least absolute shrinkage and selection operator (LASSO) regression analyses, which were selected to establish a prognostic model for glioma. Samples were divided into high- and low-risk groups, and the predictive performance of the prognostic model was evaluated based on receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) survival curves, and a nomogram. In addition, immune cell infiltration, tumor mutational burden (TMB), immunophenoscore (IPS), Tumor Immune Dysfunction and Exclusion (TIDE) and drug sensitivity were analyzed. Expression levels of selected lncRNAs and proteins were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: An 11-lncRNA signature associated with cuproptosis was established, and the risk score derived from this model was identified as an independent prognostic factor for glioma. The model exhibited excellent predictive ability, with area under the curve (AUC) values of 0.880, 0.913, and 0.866 for 1-, 3-, and 5-year survival, respectively. Higher TMB, immune checkpoint expression, and IPS were observed in the high-risk group and no significant difference was observed in TIDE between risk groups. Drug sensitivity analysis identified TPCA-1, KIN001-135, and ispinesib mesylate as potential therapeutic agents. Expression validation in glioma cells further supported the biological relevance of the selected lncRNAs. CONCLUSIONS: This cuproptosis-related lncRNA-based signature demonstrates strong prognostic value and may serve as a promising tool for glioma risk stratification and personalized treatment selection.

Glioma↗
PubMed2005

Morphine withdrawal contributes to Th cell differentiation by biasing cells toward the Th2 lineage.

The consequences that drug withdrawal has on immune functioning has only recently been appreciated; however, given the wide variety of use and abuse of opiate analgesics, understanding the decrements to immune function that withdrawal from these drugs causes is of crucial importance. In previous work, we have demonstrated that morphine treatment contributes to immunosuppression by polarizing Th cells toward the Th2 lineage. In the current study, it was hypothesized that morphine withdrawal would result in Th2 differentiation and subsequent immune dysfunction. To address this hypothesis, mice were chronically treated with morphine for 72 h followed by a 24-h withdrawal period. It was determined that 24-h morphine withdrawal resulted in a decrease in IFN-gamma, the Th1 signature cytokine, whereas the Th2 cytokine, IL-4, was increased. In addition, Western blot and EMSA experiments revealed that morphine withdrawal-induced Th2 differentiation was mediated through the classical Th2 transcription factors Stat-6 and GATA-3. In addition, the consequence of morphine withdrawal in the presence of an immune stimulation was also examined by treating mice in vivo with LPS before morphine withdrawal. Following withdrawal, it was found that the Th1-polarizing cytokine IL-12 was significantly decreased, providing further support for the observation that withdrawal results in Th2 differentiation by possibly impacting the generation of an appropriate innate immune response which directs subsequent adaptive Th1/Th2 responses.

Active Transport, Cell Nucleus↗
PubMed1997

Influence of selective decontamination of the digestive tract on cell-mediated immune function and bacteria/endotoxin translocation in thermally injured rats.

OBJECTIVE: To determine the influence of pretreatment with selective decontamination of the digestive tract (SDD) on systemic immunosuppression, and the relationship between bacteria/endotoxin translocation and abnormalities of immune function in thermally injured rats. DESIGN, MATERIALS, AND METHODS: Animals were subjected to a 40% full-thickness scald injury, and divided into SDD-treated and control groups. The treatment group received SDD (polymyxin E, tobramycin, and 5-flucytosine) by gavage twice daily for 3 days before the experiment and continued for 5 days after thermal injury. The control group was given the same amount of water. The parameters reflecting cell-mediated immunity, including splenocyte proliferation in response to mitogens, interleukin 2 (IL-2) production, and lymphocyte subpopulation, were measured before injury and 1 and 5 days after burn, respectively. MEASUREMENTS AND MAIN RESULTS: Thermal injury resulted in marked reduction in splenocyte proliferative response to T-cell mitogens, IL-2 production, and T-helper/suppressor cells (CD4/CD8) ratio. Prophylactic treatment with SDD significantly decreased the incidences of bacterial translocation and endotoxemia, prevented suppressive mitogenic response and inadequate IL-2 production (p < 0.05-0.01) but did not affect the abnormal ratio of CD4 to CD8 T lymphocytes in blood (p > 0.05). CONCLUSIONS: These results suggest that bacteria/endotoxin translocation from the gut appears to be involved in cell-mediated immune dysfunction as a consequence of thermal injury. Pretreatment with SDD might attenuate postburn immunosuppression by preventing translocation events.

Animals↗
PubMed1997

Atypical, severe toxoplasmic retinochoroiditis in elderly patients.

BACKGROUND: The diagnosis of toxoplasmic retinochoroiditis is based primarily on characteristic ocular findings, with supportive serologic evidence. Clinical recognition of atypical presentations is critical for timely antiparasitic drug therapy. METHODS: Case histories were reviewed for seven presumed immunocompetent elderly patients with atypically severe (multifocal or diffuse or both) toxoplasmic retinochoroiditis. Three cases initially were misdiagnosed as acute retinal necrosis syndrome. The correct diagnosis was confirmed in each case by response to antiparasitic drug therapy, polymerase chain reaction studies of intraocular specimens, or histopathologic analysis. RESULTS: The patients ranged in age from 69 to 82 years (median, 74 years). Only three patients had intercurrent medical conditions that may be associated with subtle immune dysfunction (diabetes mellitus and hepatitis C). The extensive necrotizing retinochoroiditis in each patient was nonhemorrhagic and not associated with occlusive retinal arteritis. Despite prompt response to antiparasitic drug therapy, prolonged treatment usually was required, and four patients had retinitis reactivation after discontinuing treatment. Significant visual loss accompanied the infection in most eyes. CONCLUSION: Toxoplasmosis should be considered as a cause of multifocal or diffuse necrotizing retinitis or both in elderly patients. Older patients may be more susceptible to severe ocular Toxoplasma infections because of age-related decline in cell-mediated immunity and chronic underlying diseases.

Aged↗
PubMed2003

Interactions between the recipient immune system and the left ventricular assist device surface: immunological and clinical implications.

The unquestionable clinical success of left ventricular assist device (LVAD) implantation has, nevertheless, been accompanied by complications arising from interactions between the implanted biomaterial and the host immune system. The aberrant state of monocyte and T-cell activation resulting from these host/device interactions is accompanied by two parallel processes: (1) selective loss of Th1 cytokine producing CD4 T-cells through activation-induced cell death; and (2) unopposed activation of Th2 cytokine producing CD4 T-cells resulting in B-cell hyperreactivity and dysregulated immunoglobulin synthesis through Th2 cytokines and heightened CD40 ligand-CD40 interactions. The net results of these events is that, on the one hand, the LVAD recipient develops progressive defects in cellular immunity and is at increased risk of serious infection, and, on the other hand, is more likely to develop allosensitization, posing a significant risk to successful transplant outcome. Intravenous immunoglobulin therapy is an effective and safe modality for sensitized LVAD recipients awaiting cardiac transplantation, reducing serum anti-human lymphoicyte antigen (HLA) alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of intravenous immunoglobulin would appear to be superior to plasmapheresis. Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized LVAD recipients of cardiac transplantation. When used after transplantation as part of triple immunosuppressive regimens, cyclophosphamide is superior to mycophenolate mofetil in reducing episodes of allograft rejection in these patients. Because these immune dysfunctions appear to be related to the effects of excessive biomaterial-associated T-cell activation, future efforts will need to be directed at either altering the physical properties of the materials interacting with the host circulation or pharmacological intervention aimed more selectively at inhibiting T-cell activation.

Heart Failure↗
PubMed2000

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗
PubMed1994

Splanchnic and systemic hemodynamic responses to portal vein endotoxin after resuscitation from hemorrhagic shock.

BACKGROUND: Hemorrhagic shock and sepsis are usually studied separately or in rodents. This study combined the two insults in a large animal model. METHODS: Anesthetized pigs were bled, held in shock for 1 hour, and then resuscitated with fluid. After 3 days, Escherichia coli endotoxin LPS was infused into the portal vein (150 micrograms/kg x 30 min) to mimic the effect of enteric substances breaching the mucosal barrier. Systemic and splanchnic hemodynamics, circulating leukocytes, and plasma levels of tumor necrosis factor (TNF) were measured in five groups: 40% hemorrhage plus fluid only resuscitation, 40% hemorrhage plus fluid-blood resuscitation, 50% hemorrhage plus fluid-blood resuscitation, sham, or sham plus 5 micrograms/kg LPS priming dose instead of hemorrhage. RESULTS: On day 4 before infusion of LPS, there were no differences between groups in hemodynamics or O2 utilization, but systemic O2 delivery and O2 consumption were each reduced in the hemorrhaged groups because of the hemodilution associated with resuscitation. For 3 hours after infusion of LPS, all animals received aggressive fluid and respiratory support, but arterial blood pressure decreased, and systemic O2 utilization, splanchnic O2 utilization, and arterial lactate level increased; there were no differences between groups. In the 50% group compared with sham, LPS-evoked decreases in cardiac index and stroke index were eliminated, and LPS-evoked tachycardia, pulmonary and systemic vasoconstriction, and increases in hepatic and portal vein lactate levels were blunted. Despite similar leukocyte counts before infusion of LPS and similar leukopenia after LPS infusion, plasma LPS level was higher in the 50% group compared with sham. Furthermore, LPS evoked increases in portal and hepatic vein plasma TNF in the shams, but those changes were reduced in the 50% group. CONCLUSIONS: Most responses to LPS were similar after hemorrhagic shock or a sham operation, which is inconsistent with the concept of "priming." LPS-evoked increases in plasma TNF were blunted after shock, probably because of trauma-induced immune dysfunction. A combined shock plus septic challenge in a large animal model may be valuable for investigating the pathogenic mechanism in human beings.

Analysis of Variance↗
PubMed1983

Aging and the mucosal-associated lymphoid system.

Several lines of evidence support the notion that the mucosal-associated lymphoid system differs from the systemic. It is possible that the mucosal lymphoid system may also differ from the systemic system with regard to immune competence with age. Our findings in these studies indicate a lack of age-associated immune dysfunction in the mucosal-associated lymph nodes: that is, mesenteric and mediastinal lymph node PFC responses of old mice that revealed no decline in magnitude were found to be highly heterogeneous with regard to antibody affinity and revealed no appreciable anti-idiotype-blocked, hapten-augmentable plaque-forming cells. By contrast, the number of splenic and, as well, draining peripheral lymph node IgM, IgG, and IgA anti-TNP PFC responses to TNP-BGG was found to decrease with age with a preferential loss of high affinity plaque-forming cells. This decline in immune activity in the systemic tissues coincided with the increased appearance of anti-idiotype-blocked, hapten-augmentable plaque-forming cells. This differential effect of aging on immune responses in vivo of mucosal and systemic lymphoid tissues imply a site preference for an age-related decline in immune function, and a division of the immune system into regulatory compartments during the normal immune response to antigen in old mice. The present demonstration of a differential effect of aging on immune function in vivo raises an important issue with regard to age-related host defense mechanisms. For example, it would seem reasonable to predict that if immune function totally wanes with age, old individuals would be greatly susceptible to disease and infection. On the contrary, host defense mechanisms relevant to infection show minimal alterations in healthy aged individuals. Thus, we believe that mucosal immunity may play a very important role in host defenses in elderly individuals.

Aging↗
PubMed1991

Pulmonary mucormycosis presenting as massive fatal hemoptysis in a hemodialytic patient with chronic renal failure.

A 38 year old female patient died following massive hemoptysis occurring during maintenance hemodialysis for chronic renal failure. In addition to renal dysfunction, laboratory data showed low levels of serum immunoglobulins; chest X-rays did not reveal any abnormal shadows. For the last 11 months, the patient had not received deferoxamine. At autopsy, major bronchi were plugged with coagulated blood. Irregular thickening of the right main bronchial wall close to the lung hilus was noted. Light microscopic examination disclosed mycotic granulomata in the bronchial wall, where the pulmonary arterial wall was also involved. Immunostaining using specific antibody identified Mucor hyphae. The mucormycosis is a serious complication of chronic renal failure and hemodialysis. In the current case, it is likely that immune dysfunction rather than deferoxamine was the important predisposing factor to the growth of the fungus.

Adult↗
PubMed1985

Viral infections in atopic dermatitis.

In a study of almost 1000 patients with past or present atopic dermatitis (AD) it was found that histories of recurrent (greater than 5 episodes/year) cold sores and upper respiratory infections, as well as histories of zoster were significantly more common in AD patients than in non-atopic controls. Serological studies revealed that AD patients have clearly elevated titers of antibodies against Epstein-Barr virus. These findings suggest that the increased susceptibility to viral infections in AD is due to immune dysfunction rather than to cutaneous alterations which are associated with the disease. The mechanisms underlying the increased susceptibility to infections may be related to immunological aberrations that are secondary to a basic abnormality in the fatty acid or cyclic AMP metabolism.

Adult↗
PubMedDate not supplied

Relation of the pathogenesis of human immunodeficiency virus infection to various strategies for its control.

This paper reviews functionally important insights into the pathogenesis of human immunodeficiency virus (HIV) infection. The major sequela of this infection is early and progressive involvement of the immune system, with widespread immune dysfunction. This pathogenetic feature has a major impact on strategies for control of the infection. The immunosuppression caused by the virus leads to higher levels of viral replication and enhanced potential for development or selection of variant viruses, including forms that are more virulent or even drug resistant. Therefore, control of HIV infection and disease may require antiviral agents and CD4 receptor competitors as well as recombinant DNA-derived lymphokines and subunit vaccine immunotherapies. To be successful, such therapies must work to counter infection in monocytes and nonlymphoid cells as well as in T4 lymphocytes. Because many limbs of the immune system are affected by HIV infection, the complexities of this pathogen can be unraveled only by the careful study of immune functions during the disease and of effective interventions to control infection and disease and to restore immune functions.

HIV↗
PubMed2001

Cytokines and chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

Cytokines↗
PubMed2003

Detrimental immunologic effects of preoperative chemoradiotherapy in advanced rectal cancer.

PURPOSE: Preoperative chemoradiotherapy for advanced rectal cancer has been an important therapeutic tool to improve the long-term results of curative resection. It is not known whether preoperative chemoradiotherapy for advanced rectal cancer influences the perioperative course of immune parameters. METHODS: Thirty patients with rectal cancer underwent surgery with (study group, n = 15) or without (control group, n = 15) preoperative chemoradiotherapy (2 cycles of 5-fluorouracil, 45 Gy). Blood samples were taken before neoadjuvant therapy, preoperatively, and on Days 1, 2, and 5 after surgery. Cell numbers of lymphocyte subpopulations, granulocytes, monocytes, and natural killer cells were determined by flow cytometry; tumor necrosis factor-alpha and interleukin-6 serum levels were measured with enzyme-linked immunosorbent assay. RESULTS: Significant differences between study and control patients (P < 0.05) were detected regarding circulating interleukin-6 and tumor necrosis factor-alpha levels, with depression of the proinflammatory response to surgery in study patients. Similarly, granulocytosis and monocytosis after surgery were significantly lower in patients after neoadjuvant therapy. Furthermore, cell counts of total T lymphocytes, T helper cells, B lymphocytes, and natural killer cells were significantly reduced after preoperative chemoradiotherapy. This depression of cell-mediated immunity in study patients was even more pronounced after surgery. CONCLUSIONS: Preoperative chemoradiotherapy for advanced rectal cancer results in a significant preoperative and postoperative immune dysfunction as indicated by depression of lymphocyte subpopulations, monocytes, granulocytes, and proinflammatory cytokine release. These findings are of importance because increased perioperative morbidity and mortality rates have been observed after preoperative chemoradiotherapy.

Aged↗
PubMed1996

Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison.

In the disease of endometriosis, endometrial tissue grows outside the uterus, usually in the peritoneal cavity. Rodent models of endometriosis allow a way to reproduce the disease, evaluate effects of chemicals, and study mechanisms. Twenty-one days prior to induction surgery which produces endometriosis, female Sprague-Dawley rats and B6C3F1 mice were pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 0, 3 or 10 micrograms TCDD/kg. Animals were treated again at the time of surgery and at 3, 6, and 9 weeks following surgery. Evaluations were made at 3, 6, 9, and 12 weeks postsurgery. TCDD produced a dose-dependent increase in endometriotic site diameter when all time points were pooled within each dose in rats and a dramatic increase in site diameter in mice at 9 and 12 weeks. In rats but not mice, ovarian weight was decreased at 9 and 12 weeks, the occurrence of persistent vaginal estrus was increased at these times, and histological evaluation of the ovaries revealed ovulatory arrest at 12 weeks. In both species, thymic antrophy, indicating immune dysfunction, and hepatomegaly were observed as consequences of TCDD exposure. Body weight was reduced in rats but not in mice. Histological evaluations of endometriotic sites revealed fibrosis in control rats, necrotic and inflammatory changes in the sites from TCDD-treated rats, and predominantly fibrotic changes in sites from TCDD-treated mice. Differences observed between the rat and the mouse with respect to (a) the magnitude of the effect on endometrial site diameter (rats < mice), (b) measured effects on ovarian function (rats > mice) that may be based on the partial antiestrogenicity of TCDD, and (c) evidence that mice and rats differ in their immune response to TCDD suggest that the mechanisms mediating TCDD's action to promote endometriosis are complex and may be different in rats and mice. The mouse may be a better model for future studies necessary to elucidate these mechanisms.

Animals↗