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R A Daynes

Publications and source records attributed to R A Daynes.

At least 37 records · Page 2Linked to original sources
PubMed1996

11 beta-hydroxysteroid dehydrogenase modulation of glucocorticoid activities in lymphoid organs.

The immunoregulatory effects of glucocorticoids (GCS) are linked to their capacity to alter the production of various species of cytokines associated with immune and inflammatory processes. The present study determined that the influences of GCS within particular lymphoid organs vary, depending on the specific activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) within the tissue. This enzyme converts active GCS to inactive metabolites and was found to display greater activity in peripheral than in mucosal lymphoid organs. A direct correlation was found between 11 beta-HSD activity and the preferential production of type 1 cytokines by T-cells residing within certain lymphoid organs. It was established that lymphoid organ 11 beta-HSD was localized in the immobile stromal cell components. Inhibition of 11 beta-HSD activity in vivo reduced type 1 and enhanced type 2 cytokine production by activated T-cells, and it also depressed the ability of animals to generate contact hypersensitivity responses. We conclude that GCS levels can be controlled within lymphoid organs through oxidative inactivation by 11 beta-HSD. GCS action is, therefore, dependent on tissue levels of 11 beta-HSD activity, the number of GCS receptors in a responsive cell, and the concentration of circulating GCS.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal injury.

Progressive ischemia and necrosis of the skin following thermal injury are reduced by postburn administration of the steroid hormone dehydroepiandrosterone (DHEA). Thermally injured animals were provided with a subcutaneous injection of DHEA, or a related species of steroid hormone, at various times after burning. During the 96 hr following administration of the scald burn, tissue necrosis was closely monitored. Subcutaneous administration of DHEA at approximately 1 mg/kg/day achieved optimal protection against the development of progressive dermal ischemia. DHEA, 17 alpha-hydroxy-pregnenelone, 16 alpha-bromo-DHEA, and androstenediol each demonstrated, a similar level of protection. Other forms of steroids, including DHEA sulfate, androstenedione, 17 beta-estradiol, or dihydrotestosterone, exhibited no protective effect under the conditions tested. Additionally, intervention therapy with DHEA could be initiated up to 4 hr, but not 6 hr, after burn without a marked reduction in therapeutic benefit. Examination of the microvasculature of thermally injured dorsal skin suggested that postburn intervention with DHEA, either directly or indirectly, maintained a normal architecture in most of the dermal capillaries and venules within burn-exposed tissue. These findings suggest that systemic intervention therapy of burn patients with DHEA or a similar acting steroid hormone may be useful in preventing the progressive tissue destruction caused by progressive ischemia.

17-alpha-Hydroxypregnenolone↗
PubMed1995

Th1/Th2-like immunity and resistance to herpes simplex labialis.

To investigate potential immunologic mechanisms of resistance to recurrent herpes simplex labialis, we assayed serum antibody titers and cultured peripheral blood mononuclear cell (PBMC) cytokine production among patients with a history of frequent episodes (H+S+), herpes simplex virus (HSV)-seropositive individuals without a history of herpes labialis (H-S+) and HSV-seronegative persons (H-S-). In addition, H+S+ patients were exposed to experimental ultraviolet radiation (UVR) on the lips and the immunologic assay results compared among those who developed experimental lesions and those who did not. H+S+ patients were found to have higher median serum titers of HSV antibody and trends to lower levels of HSV-specific PBMC IFN-gamma and IL-2 than H-S+ control patients (123 vs 66, P = 0.04; 424 vs 548 pg/ml, P = 0.08; 14 vs 26 pg/ml, P = 0.14, respectively). Correlation of the results with the occurrence of experimental lesions showed the inverse: the subgroup of H+S+ patients with UVR-induced lesions had lower titers of antibody and trends to higher levels of IFN-gamma and IL-2 than H+S+ patients who could not be induced (93 vs 149, P = 0.02; 501 vs 347 pg/ml, P = NS; 26 vs 11 pg/ml, P = NS, respectively). The size and duration of UVR-induced lesions showed positive correlations with IFN-gamma and IL-2 levels (r = 0.60-0.67, P = 0.02-0.04). Although the small number of patients limited the power of this study, the overall pattern of the findings suggests that a Th1-like cytokine response (IFN-gamma and IL-2 production) may be associated with resistance to naturally occurring episodes of herpes labialis. The development and severity of experimental UVR-induced herpes labialis appears to be regulated differently and may involve an immunopathologic mechanism.

Antibodies, Viral↗
PubMed1995

Steroids as regulators of the mammalian immune response.

The mammalian immune system is multicellular in composition, and its proper function requires careful control over complex developmental pathways and many distinct types of effector responses. Numerous overlapping mechanisms of intercellular communication are needed to accomplish the tasks of proper regulation of the diverse cell types that constitute this essential protective system. One mechanism occurs by direct cell-to-cell contact through the interaction of membrane-associated molecules. Examples of this type of communication include the interaction that takes place between the antigen-specific T-cell receptor and the foreign peptides that are bound to major histocompatibility complex molecules, as well as costimulatory molecule interactions with their specific ligands expressed on antigen-presenting cells (e.g., CD28 and B7-1 or B7-2). A second mechanism occurs through the production, secretion, and activities of soluble mediators, collectively known as the cytokines. The cytokines are represented by a large and diverse group of molecules that are produced by a wide variety of cell types. Unique species of cytokines bind to specific membrane-associated receptors on target cells, inducing the activation of particular signal-transduction pathways. These processes subsequently lead to the diversity of cytokine-linked changes in cellular physiology. Some of the cytokines exert their influences in vivo via endocrine routes, although it is far more common for intercellular communication via cytokines to occur microenvironmentally via paracrine or autocrine pathways. The object of this review is to provide evidence supporting the concept that one mechanism for upstream regulation of cytokine production by immunocompetent cell types is controlled by the regulatory activities of various steroid hormones. Strain variation in susceptibility to infectious agents, the condition of immunosenescence, and the processes that control the development of common mucosal immunity are used as examples of immune mechanisms that may be under steroid hormone control.

Aging↗
PubMed1995

Fetal outcome in murine Lyme disease.

Lyme disease is an inflammatory syndrome caused by infection with Borrelia burgdorferi. Although this syndrome has important implications for human pregnancy, little is known about gestational infection with B. burgdorferi. Fetal death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice infected by intradermal injection of B. burgdorferi 4 days after mating (acute infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty-six percent of acutely infected mice suffered at least one fetal death, compared with none of the control animals (P = 0.0002). There were no fetal deaths in 18 C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice but did not detect DNA in the uteri of controls or chronically infected mice. Spirochete DNA was only rarely detected in fetal tissues, and its presence was not required for fetal death. The inclusion of an internal competitive PCR target indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to the presence of a PCR inhibitor. Histologic analysis of gestational tissues from infected animals demonstrated nonspecific pathology consistent with fetal death. These findings indicate an association between murine fetal death and acute infection with B. burgdorferi early in gestation but not with chronic infection. Our data suggest that fetal death is due to a maternal response to infection rather than fetal infection. These findings could provide an explanation for observations in humans in which sporadic cases of fetal death in women infected with B. burgdorferi during pregnancy have been reported, while previous infection has not been associated with fetal death.

Animals↗
PubMed1994

The development of effective vaccine adjuvants employing natural regulators of T-cell lymphokine production in vivo.

Steroid hormones are important regulators of gene function in vivo. A number of naturally occurring species of steroid hormones are able to qualitatively and quantitatively influence the production of lymphokines by activated T cells in vitro. Similar mechanisms are probably also occurring naturally in vivo and could explain why mucosal and nonmucosal lymphoid organs harbor T cells having unique potentials for lymphokine production. It was established that the topical application of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) to normal mice changed the pattern of lymphokines produced by activated T cells isolated from the draining peripheral lymph nodes. The hormone-treated T cells produced a pattern of lymphokines similar to that normally found in Peyer's patches. Subcutaneous vaccination with a protein antigen, in a site afferent to 1,25(OH)2D3-manipulated lymph nodes, resulted in an enhanced serum antibody response and was uniquely capable of also stimulating a common mucosal immune response to the antigen as well. Common mucosal immunity was confirmed by demonstrating the presence of antigen-specific IgA and IgG responses in a number of mucosal secretions and by further establishing that antibody-secreting plasma cells had migrated to the lungs and small intestines of the hormone-treated and vaccinated animals. Additional experiments established that common mucosal immunity could also be induced in aged animals as long as the immune system of the vaccinated animals was functioning normally. This was accomplished by providing the aged animals with a dietary supplement of dehydroepiandrosterone sulfate (DHEAS). Previous studies by us have documented that aged animals provided with replacement levels of DHEAS, a natural steroid hormone whose endogenous production declines with advancing age, are able to mount normal systemic humoral and cellular immune response following subcutaneous vaccination with a variety of protein and polysaccharide antigens. The combination of supplemental DHEAS therapy with topical 1,25(OH)2D3 treatment at the time of vaccination provided the conditions needed to generate mucosal and systemic immune responses to inactivated influenza virus antigen by old animals.

Adjuvants, Immunologic↗
PubMed1994

Dietary restriction from middle age attenuates age-associated lymphoma development and interleukin 6 dysregulation in C57BL/6 mice.

Dietary restriction (DR) started in middle age profoundly reduces the occurrence of lymphoma in C57BL/6 mice. Here, we report immunocellular and molecular changes associated with this mode of cancer prevention. Twelve-month-old male C57BL/6 mice were either fed a control diet or subjected to moderate DR (approximately 25% < control intake). DR significantly reduced lymphoma development (incidence at 25 months, 19% of 72 control mice versus 5% of 60 DR mice). Flow cytometry of splenocytes showed that DR increased the percentage of CD4+ and CD8+ cells. Lymphomatous spleens displayed varied labeling patterns and high percentages of cells in S phase. Splenocyte c-myc expression tended to increase with age in controls and was reduced by DR. Lymphopenia and markedly reduced nucleated cell yields from peripheral lymphoid tissues were induced by DR. Serum interleukin 6 levels increased with age and were quite high (> 2500 pg/ml) in several mice with lymphoma and other histopathological findings. DR attenuated this age-associated increase. Immunohistochemical studies of lymphomatous spleens showed the presence of interleukin 6 in monocytic appearing cells but not in lymphoma cells. These observations support the possibility that an age-associated interleukin 6 dysregulation is important in lymphomagenesis.

Age Factors↗
PubMed1994

Age- and microenvironment-associated influences by platelet-derived growth factor on T cell function.

Platelet-derived growth factor (PDGF) is produced by numerous cell types in response to a variety of activation signals. Although the role of PDGF in cellular proliferation is well established, the immunomodulatory effects of this peptide growth factor are only now being delineated. We previously established that PDGF alters the profile of lymphokines produced by activated T cells obtained from the peripheral lymph nodes of adult mice. We now report that T cells residing in lymphoid organs that receive their major afferent lymphatic drainage from gut mucosa are relatively resistant to the effects of this growth factor. As the vast majority of peripheral T cells are in the recirculating T cell pool, these findings suggest that tissue-specific microenvironmental factors function to regulate the sensitivity of T cells to PDGF-mediated influences. Additional studies have determined that the normal process of aging is accompanied by a systemic loss in T cell responsiveness to PDGF. Although the T cells of immature (2-wk-old) and young adult mice are responsive to the immunomodulatory influences of PDGF, T cells of aged animals (> 100 wk) are relatively resistant to its effects. Some of the immune abnormalities noted to occur during the aging process appear to represent a consequence of the dysregulated production of IL-6. We therefore evaluated whether IL-6 was responsible for modifying the sensitivity of T cells to PDGF. Data presented herein demonstrate that IL-6 abrogates the ability of PDGF to modify lymphokine production by T cells after activation. Therapeutic measures capable of reducing spontaneous IL-6 production in aged mice restored the ability of their T cells to respond to PDGF, suggesting that the dysregulated production of IL-6 within the aged host interferes with the ability of PDGF to convey important microenvironmental information to T cells residing in peripheral lymphoid organs.

Aging↗
PubMed1994

Lipopolysaccharide-induced fetal death: the role of tumor-necrosis factor alpha.

Lipopolysaccharide (LPS) administration has been known to cause murine fetal death for over 50 years, but the responsible mechanism(s) remains unclear. We used the LPS-hyporesponsive murine strain, C3H/HeJ, to 1) establish whether LPS-induced fetal death is due to a maternal or fetal response to LPS and 2) to investigate the involvement of tumor necrosis factor alpha (TNF alpha) in fetal death caused by LPS. C3H/HeJ (LPS-hyporesponsive) or C3H/HeN (LPS-responsive) females were mated with C57B1/6 or C3H/HeN males (both LPS-responsive). Administration of 10 micrograms LPS caused fetal death in C3H/HeN mothers. However, up to 1000 micrograms LPS did not result in the death of LPS-responsive fetuses when administered to C3H/HeJ mothers. Systemic administration of TNF alpha was able to cause fetal death in both C3H/HeN and C3H/HeJ strains of mice. Pretreatment of pregnant C3H/HeN mice with anti-TNF alpha antibodies significantly reduced fetal death caused by LPS administration. The administration of a sublethal dose of TNF alpha plus 10 micrograms LPS to pregnant C3H/HeJ mice restored abortifacient activity. These results indicate that LPS-induced fetal death is due to a maternal response as opposed to a direct fetal response to LPS and that TNF alpha appears to be an important mediator of fetal death caused by LPS.

Animals↗
PubMed1994

Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines.

Metabolism of dehydroepiandrosterone sulfate (DHEAS) to dehydroepiandrosterone (DHEA) occurs within specific anatomical compartments in vivo through the actions of the enzyme DHEAS sulfatase. This enzymatic activity facilitates the conversion of hydrophilic DHEAS to the hydrophobic species DHEA, which can then be further metabolized to other steroid hormones. High levels of DHEAS sulfatase reside in tissues where the biological activity of DHEA or its downstream metabolites regulate cellular function. Therefore, control over the activity of DHEAS sulfatase may represent an important regulatory process for the production of DHEA and its metabolites. Homogeneous populations of macrophages from normal mice were found to effectively convert DHEAS to DHEA in vitro. DHEAS sulfatase activity could be markedly depressed after exposure of these cells to a variety of nonspecific macrophage activators [i.e. zymosan, polyinosine/cytosine, heat-killed bacteria, or bacterial lipopolysaccharide (LPS)]. Inhibition of DHEAS metabolism was found to require protein synthesis, because temporary abrogation of protein synthesis with cycloheximide eliminated the ability of LPS to depress the conversion of DHEAS to DHEA. Additionally, exposure of LPS-nonresponsive macrophages to supernatants derived from LPS-treated BALB/c macrophages inhibited their ability to convert DHEAS to DHEA. Potent inhibition of sulfatase activity could be achieved by directly exposing murine macrophages to interferon-alpha (IFN alpha), IFN beta, or tumor necrosis factor-alpha, but not interleukin-1, interleukin-6, granulocyte-macrophage colony-stimulating factor, transforming growth factor-beta, platelet-derived growth factor, or the T-cell product IFN gamma. Our results indicate that macrophage metabolism of DHEAS to DHEA is down-regulated after cellular activation. Furthermore, inhibition of DHEAS sulfatase activity appears to be mediated through the actions of the inflammatory cytokines tumor necrosis factor-alpha and IFN alpha/beta.

Animals↗
PubMed1993

Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative.

Normal aging in humans has been recently shown to be accompanied by reduced control over production of the multifunctional cytokine IL-6. This cytokine was reported to be quantitatively elevated in most serum samples obtained from "normal" elderly humans. In the present investigation, we report that IL-6 levels are elevated in serum samples obtained from aged mice, and its spontaneous production could also be easily detected in culture supernatants of unstimulated lymphoid cells obtained from aged, but not mature, adult donors. Spontaneous production of IL-6 was consistently observed in culture supernatants of lymphoid cells from both the spleen and mesenteric lymph nodes from aged donors, but was absent from supernatants derived from their peripheral lymph nodes. In aged mice, the reduced regulation of IL-6 production could be effectively prevented and/or reversed by supplementing aging animals with dehydroepiandrosterone sulfate, a steroid hormone whose endogenous production is known to decline with advancing age in all species tested. It was also established that serum obtained from old dehydroepiandrosterone sulfate-treated mice contained lower (normal) levels of serum amyloid P substance (an acute phase reactant), reduced levels of serum Ig (all classes and isotypes) and lower titers of tissue-specific autoantibodies than untreated aged controls. Therefore, a number of well described, age-related conditions, some of which could be contributing to the pathologic phenotype of old age, may actually represent secondary effects to this age-associated change in IL-6 production.

Aged↗
PubMed1993

Administration of dehydroepiandrosterone to burned mice preserves normal immunologic competence.

Burned individuals display a reduced ability to elicit cellular and humoral immune responses and a depression in the vitro production of certain T-cell lymphokines. Treatment of burned mice with 100 micrograms of dehydroepiandrosterone within 1 hour after injury resulted in preserving a completely normal capacity to produce T-cell-derived lymphokines and to generate cellular immune responses. In addition, dehydroepiandrosterone-treated thermally injured mice demonstrated an above-normal ability to resist an induced infection with the intracellular pathogen, Listeria monocytogenes. Dehydroepiandrosterone-treated animals also did not exhibit the sustained plasma levels of interleukin 6 that normally accompany thermal injury and infection. Because of its antiglucocorticoid effects and positive immunoregulatory influences, we believe dehydroepiandrosterone to be a beneficial form of therapy for thermally injured individuals.

Animals↗
PubMed1993

Adaptive immune responses during murine pregnancy: pregnancy-induced regulation of lymphokine production by activated T lymphocytes.

OBJECTIVE: We hypothesized that the lymphokine production by splenocytes and decidual lymphocytes would be altered because of changes in immunoregulation during pregnancy. STUDY DESIGN: Splenocytes and decidual lymphocytes were isolated from syngeneic and allogeneic pregnant mice at different times of gestation. The lymphocytes (10(7) cells/ml) were stimulated with anti-CD3 antibody, and culture supernatants were assayed for several lymphokines, including interleukin-2, interferon-gamma, interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3. Statistical analysis was by analysis of variance or paired t test. RESULTS: Activated splenocytes produced significantly less interleukin-2 and more interleukin-4, interleukin-6, and interleukin-3 as murine pregnancy advanced. Production of interferon-gamma and granulocyte macrophage colony-stimulating factor by activated splenocytes peaked in the first 8 to 14 days of pregnancy. Stimulated decidual lymphocytes produced modest amounts of interleukin-6, granulocyte-macrophage colony-stimulating factor, and interleukin-3 during pregnancy but no interleukin-2, interferon-gamma, or interleukin-4. Similar results were found for both syngeneic and allogeneic matings. CONCLUSIONS: Our findings indicate that splenocyte lymphokine production favors interleukin-4 production over interleukin-2 production. This finding suggests that antibody production would be enhanced and cytotoxic cellular immune responses inhibited during pregnancy. These changes occurred regardless of mating partner, suggesting that the specific antigenic stimulus during normal pregnancy does not regulate lymphokine production. Activated splenocytes and decidual lymphocytes were found to differ in their capacity to produce lymphokines, indicating that the decidua constitutes a distinct and unique immunologic microenvironment.

Animals↗
PubMed1993

Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen.

This study sought to establish whether administration of dehydroepiandrosterone (DHEA) or its sulfate derivative to aged mice could effectively correct the immunosenescent phenotype. Supplemental DHEA sulfate and topical DHEA fully corrected the age-associated dysregulated production of T cell lymphokines by cells from all of the different lymphoid organs tested. Either DHEA or DHEA sulfate supplementation promoted enhanced antibody responses against recombinant hepatitis B surface antigen (rHBsAg) by the aged recipients when incorporated directly into the vaccine. When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration. It was also established that DHEA treatment could enhance specific antibody responses to rHBsAg in aged animals that had previously not been effectively immunized by conventional vaccination procedures.

Adjuvants, Immunologic↗
PubMed1993

Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction.

Interleukin-6 (IL-6) is a multifunctional cytokine that is proving to be a major contributor to the acute phase inflammatory response. IL-6 expression is normally low and serum levels are usually nondetectable in the absence of inflammation. With advancing age, however, serum levels become detectable and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this report we demonstrate that plasma levels of IL-6 rise with advancing age in well-selected healthy elderly people and comparably in old rhesus monkeys. That this change reflects a primary aging process is suggested by our findings in C57BL/6 mice in which the age-associated increase in the in vitro synthesis of IL-6 is largely prevented by life span-extending dietary restriction.

Adult↗
PubMed1992

The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells.

We have investigated the ability of dehydroepiandrosterone (DHEA) to alter the production of interleukin-2 (IL-2) and to bind to a specific binding complex in antiCD3 epsilon activated T cells. Binding activity correlated with the presence of a specific DHEA binding complex in the cytosol and nuclei of DHEA-responsive T-cell hybridomas, as well as in CD4+ and CD8+ cells isolated from peripheral lymph nodes of normal mice. Scatchard analysis determined that intact lymphocytes and cytosolic fractions contained high affinity binding for [3H]DHEA (approx. 2.6 nM) with 1000-7000 binding sites existing per cell. Five of the T-cell hybridomas tested both responded to DHEA treatment with increased production of IL-2 and also contained specific high affinity [3H]DHEA binding. Four additional T-cell hybridomas were found to contain no specific [3H]DHEA binding and were also unresponsive to DHEA influences on IL-2 production. Sucrose density gradients demonstrated a 3-4s [3H]DHEA binding complex in high salt and a 7-8s binding complex in low salt. Specific binding was inhibited by preincubation of the cytosol fractions with either trypsin or chymotrypsin, or by heating to 60 degrees C for 1 h (less than 15% of control). [3H]DHEA binding was unaffected by preincubation of the cytosol fractions with ribonuclease, deoxyribonuclease, or phospholipase A. The DHEA-protein complexes bound to DNA-cellulose with the amount of binding being slightly increased by preincubation at 25 degrees C as compared to 4 degrees C. As expected, [3H]DHEA binding was inhibited by the addition of unlabeled DHEA, but was also modestly inhibited by dihydrotestosterone and cortisol. Binding of DHEA was unaffected by progesterone, dexamethasone, estradiol, androsterone, DHEAS, and beta-etiocholanolone at all concentrations tested. DHEA was incapable of inhibiting the binding of [3H]DHT to the androgen receptor or [3H]dexamethasone to the glucocorticoid receptor. Collectively, these findings suggest that murine T cells contain a specific DHEA receptor. We believe that DHEA is a steroid hormone that is directly involved in the regulation of IL-2 production by both normal and some T-cell hybridomas.

Animals↗
PubMed1992

Natural regulators of T-cell lymphokine production in vivo.

The mammalian immune system possesses the intrinsic capacity to evoke a wide variety of functionally distinct effector mechanisms following stimulation by a particular antigenic substance. Such diversity in available responses is absolutely essential to the immunocompetent host, which must continually deal with a diverse set of potential pathogens within its ever-changing environment. The development of appropriate types of immune responses, therefore, represents a highly dynamic process that requires that an equivalent consideration be given to a large array of components, any one of which is capable of modulating the final outcome. While the nature and complexity of the antigen(s), plus the intracellular or extracellular mode of presentation, provide specificity and some selection to the developing process, the route of antigen entry, as well as the physiological status of the host at the time of antigen insult, also contribute significantly to the formation of any immune response. The overall objective of this article is to introduce the concept that platelet-derived growth factor (PDGF) (either preformed or synthesized in response to stimulation), plus a number of steroid hormones (some of which are end-organ metabolized at local tissue sites), can all play significant roles in the genesis of immunologic responses in vivo.

Aging↗