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[Generalized granuloma annulare or diffuse dermal histiocytosis?].

Generalized granuloma annulare is a rare variant of granuloma annulare affecting the trunk and extremities with a multitude of lesions. In contrast to localized granuloma annulare, generalized granuloma annulare occurs in older patients, shows a stronger association with diabetes, and is characteristically chronic. Like our 55-year-old patient, most patients present with papules and annular plaques; less often, macular or non-annular lesions may be encountered. Histology often fails to show necrobiotic or necrotic connective tissue changes demarcated by a palisading granuloma. Instead, there are diffuse dermal, band-like or nodular aggregations of histiocytes intermingled with some multinucleated giant cells and a predominantly lymphocytic infiltrate in the periphery. Because of its special characteristics, it has been suggested that generalized granuloma annulare might constitute a separate disease entity and that it should be classed among the primary cutaneous histiocytoses as a diffuse dermal histiocytosis. Using immunohistochemistry to determine the macrophage phenotype of the lesional histiocytes, we have shown that generalized granuloma annulare is not a cutaneous histiocytosis. Neither MS-1 high-molecular-weight protein, a new specific marker for cutaneous non-Langerhans cell histiocytoses, nor CD1a, the well-known marker for Langerhans cells and Langerhans cell histiocytoses, is expressed by the lesional histiocytes of our patient. In contrast, the antigen expression pattern was diagnostic for non-infectious granulomas and was highly similar to that in localized granuloma annulare. In contrast to the successful treatment of localized granuloma annulare reported with intralesional interferon beta-1, systemic treatment with interferon alpha-2b (9 x 10(6) units three times a week) was ineffective.

Biopsy↗

Spermatic granuloma of vas deferens after vasectomy in rhesus monkeys and men: light and electron microscopic study.

Spermatic granuloma of the vas deferens is a common complication of vasectomy which has received scant morphologic study. This study investigated the light and electron microscopic structure of such granulomas detected in rhesus monkeys (Macaca mulatta) and man after various modes of vasectomy and postoperative periods. Unilateral experimental vasectomy in monkeys was performed by either silk ligation or clasp occlusion; in 4 of 13 ligated animals and 5 of 5 clasp vasectomized animals granulomas developed at the site of fasectomy. In man, portions of the vas deferens were excised adjacent to the site of vasectomy preparatory to vasovasostomy. Of 5 patients studied, unilateral spermatic granulomas developed in 3. Such granulomas in both monkey and man were characterized by (1) masses of sperm surrounded by epithelioid cells and connective tissue, and (2) multiple epithelial-lined channels which often contained sperm and spermiophages. In both species, fine structural characteristics of the epithelium lining such channels closely resembled those of the principal cells of the normal vas. Spermiophagic cells included macrophages, epithelioid cells, and, in the monkey only, neutrophils. Lymphocytic invasion was a common feature of the human granulomas but was found only occasionally in the monkey granulomas. As a greater number of granulomas are studied in humans and monkeys, it is hoped that the processes underlying granuloma formation and the role of such granulomas in the development of complications after vasectomy will be clarified.

Animals↗

Hepatic granulomas in children. A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma.

In a 15-year period at the Riley Hospital for Children, granulomas were found in 23 (4%) of a total of 521 liver biopsies. An etiology was identified in 87%: Histoplasma was diagnosed in 15 cases (65%) by polymerase chain reaction (PCR) on paraffin-embedded tissue, serology, and special stains; sarcoidosis was diagnosed in four cases; and schistosomiasis was diagnosed in one case. Serial liver biopsies were available from five patients; granulomas occurred in only one biopsy of the series from each patient. Extrahepatic tissue from six patients contained granulomas, and an etiology for the liver granulomas was identified in all six patients (four histoplasmosis, two sarcoidosis). The extrahepatic tissue from two patients with Histoplasma was diagnostic. We made the following conclusions: that PCR is applicable to archival material and greatly increases the yield of specific infectious diagnoses of liver granulomas compared with conventional diagnostic methods (65 versus 22%); that the infections causing liver granulomas are those that are endemic in a community (e.g., Histoplasma in Indiana); that Histoplasma can coexist with a wide variety of systemic and primary liver diseases; that the likelihood of identifying a cause of liver granulomas is increased if there are extrahepatic granulomas; and that hepatic granulomas may have a limited life span. Treatment of liver granulomas should be determined by the clinical setting and directed at the underlying cause.

Adolescent↗

NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease.

OBJECTIVES: The etiology and mechanism leading to granuloma formation in patients with Crohn's disease (CD) are presently unknown. The first susceptibility gene to be identified as a risk factor for CD is the NOD2/CARD15 gene on Chromosome 16. Mutations in NOD2 could affect the intracellular response to bacterial products and may eventually lead to granuloma formation. The association between NOD2 and granulomas has not been previously explored. We evaluated a possible association between NOD2 mutations and granuloma formation, and compared the prevalence of granulomas in both pediatric and adult cohorts. METHODS: Patients were consecutively recruited through pediatric gastroenterology and adult gastroenterology programs. Patients were eligible if CD was confirmed, and they had undergone full colonoscopy with biopsy and/or surgical resection. Patients underwent genotyping for NOD2 disease-associated mutations. RESULTS: A total of 230 patients were enrolled into the study, of whom 169 patients met all inclusion/exclusion criteria (Group 1, 77 patients [age range 1-16 years]; Group 2, 92 patients [age range 17-68 years]). Surgical resection was performed more often in adults (P < 0.005), and gastroscopy was performed more frequently in children (P < 0.001). Granulomas were found in 34% of the patients studied. The prevalence of granulomas did not differ by age, age group, or gender. A disease-associated NOD2 mutation was found in 37.8% of patients. Granulomas were found in 39% of patients with NOD2 mutations compared with 31% of those without NOD 2 mutations (difference was not significant). In addition, no difference was noted for the specific mutations. CONCLUSIONS: We did not find any correlation between NOD2 mutations and granuloma formation. The cause of granulomas in CD remains elusive.

Adolescent↗

Role of T cells in granuloma formation induced by Rhodococcus aurantiacus is independent of their interferon-gamma production.

Intravenous injection of Rhodococcus aurantiacus into mice causes granulomatous inflammation dependent on endogenous interferon-gamma (IFN-gamma). This study investigated the mechanism of granuloma formation with an adoptive transfer system in IFN-gamma knockout (IFN-gamma(-/-)) mice. IFN-gamma(-/-) mice infected with R. aurantiacus did not develop granulomas, and high titres of endogenous interleukin-10 (IL-10) were detected in spleen extracts at 2 weeks after infection. The adoptive transfer of splenocytes from infected wild-type (IFN-gamma(+/+)) mice did not restore granuloma formation, although this treatment diminished IL-10 production in IFN-gamma(-/-) mice. Adoptive transfer of splenocytes from infected IFN-gamma(-/-) mice into infected IFN-gamma(+/+) reduced granuloma formation. These results suggest that splenocytes of IFN-gamma(-/-) mice suppress granuloma formation. On the other hand, although IFN-gamma production induced by R. aurantiacus infection was detected in nude mice, which are deficient in T cells, granuloma formation was not induced in them. However, adoptive transfer of immune splenocytes from either IFN-gamma(+/+) mice or IFN-gamma(-/-) mice could induce granuloma formation. This means that splenocytes of IFN-gamma(-/-) mice have the ability to both induce and suppress granuloma formation. Induction of granuloma is probably dependent on both T cells and IFN-gamma produced by non-T cells. It is suggested that the role of T cells in granuloma formation is not dependent on their IFN-gamma production.

Actinomycetales Infections↗

Autotransplantation of hepatic granulomas into the skin of mice with Schistosoma mansoni infection.

Hepatic egg granulomas of mice infected with Schistosoma mansoni were transplanted into the skin of the same animal and changes occurring to macrophages, eosinophils, and mast cells over time were studied by light and electron microscopy and by autoradiographic techniques. Disappearance of cellular components about the egg granulomas occurred within 1 week; the entire implant became encapsulated by inflammatory cells and stroma. By 3 weeks mononuclear cells and macrophages reorganized the granulomas around the eggs and neutrophils disappeared. Activated macrophages contained both secretory rough endoplasmic reticulum and lysosomal-dense bodies. Granuloma size increased up to 5 weeks after implantation and mast cells and eosinophils tended to migrate into the granulomas. The mast cell index always remained lower than in the original hepatic granulomas, while eosinophils were seen in large numbers. During 3 to 8 weeks after implantation mononuclear cells undergoing DNA synthesis in the granulomas ranged from 2.9-4.8%. Some 3-week-old autotransplants were injected with 3H-thymidine and biopsied from 1 to 21 days later. Labeled mononuclear cells peaked in the granulomas by 10 days (24%) and the numbers fell off sharply after that. These findings indicate that autologously implanted schistosome egg granulomas can be maintained successfully in the skin for prolonged periods with marked ingress of macrophages and eosinophils. The autoradiographic data suggest the lesions are high turnover granulomas.

Animals↗

Alumina cream-induced focal motor epilepsy in cats. Part 5. Excision and transplant of the epileptogenic granuloma.

The role of alumina cream (AC) epileptic granulomas in producing clinical convulsions and EEG spikes was evaluated by excising and transplanting such granulomas from donors to recipient cats. In donors, granulomas were produced by single microinjections of AC into the right motor cortex and were subsequently excised during latent premature (P), mature (M), convulsive, and remission stages. The excised granulomas from donors were homogenized and injected into the homologous cortices of the recipient cats. The epileptogenic effect of the AC granuloma transplant in the recipients and the antiepileptogenic effect of the AC granuloma excision in the donors were evaluated by the presence or absence of clinical convulsions and the maximal EEG spike density at the right motor cortex (MSD) after lesion excision and transplant. In addition, a correlation between MSD (spikes/10 min) of donors and recipients and the aluminum content (microgram/ml) in granuloma and perilesional cortex of control epileptic cats (neither excised nor transplanted) was established during latent P, M, convulsive, and remission stages. The epileptogenic effect of AC granulomas transplanted into recipients was significantly larger when they were excised from donors in latent P and M than in convulsive, and in convulsive than in remission. The antiepileptogenic effect of AC granuloma excision in donors was significantly larger in latent P than in latent M and convulsive, and in convulsive than in remission. The aluminum content of AC granuloma and perilesional and contralateral cortices in controls was significantly larger in latent P and M than in convulsive and in convulsive than in remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Association of intestinal granulomas with smoking, phenotype, and serology in Chinese patients with Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a heterogenous disease characterized by variable manifestations and outcomes, and increasing in incidence in China. Phenotypic classification has been proposed to assist in subtyping of disease. Non-caseating intestinal granulomas are a hallmark of CD, but whether intestinal granulomas help predict Chinese CD phenotypes or determine severity, is not known. AIMS: To determine the association between intestinal granulomas with CD phenotype, severity, risk factors, and serological markers. METHODS: This was a single-centre study of consecutive definite Chinese CD cases. Granulomas were diagnosed by an experienced GI pathologist. Correlation with the Vienna Classification and other parameters was performed. RESULTS: Eighty Chinese CD patients were recruited, 40 (50%) of whom had intestinal granulomas. Intestinal granulomas were independently associated with the stricturing behavior (OR: 4.71; 95% CI: 1.41-15.72), colonic location of disease (OR: 26.96; 95% CI: 2.68-271.14), but not with age of CD diagnosis. Current or previous smoking protected against the development of granulomas (OR: 0.16; 95% CI: 0.04-0.59). Granulomas were not associated with peri-anal involvement, extra-intestinal manifestations, anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae antibody serology, or severity of CD gauged by the requirement of major intestinal surgery or immunomodulating therapy. CONCLUSIONS: Intestinal granulomas in the setting of CD may be helpful in determining phenotypic subtypes of CD, but is unhelpful in predicting disease severity. Smoking impairs the formation of granulomas in CD.

Adult↗

Granuloma cytokines in murine cysticercosis.

Neurocysticercosis, caused by Taenia solium, is one of the most common causes of seizures worldwide. The symptoms result from granulomatous inflammation associated with dying cyst forms of the parasite. Although the invasive larvae can be killed by immune serum plus complement, immunity to the cyst stage depends on a cellular response. This dichotomous immune response is reminiscent of the extremes of the immune response associated with T helper 1 (Th1) and Th2 cytokine profiles. To characterize the cytokine response in cysticercosis, granulomas were removed from the peritoneal cavity of mice infected with Taenia crassiceps cysts and examined for cytokine message by in situ hybridization using 35S-labeled RNA probes. The granulomas were staged based on histologic appearance of the degenerating parasite. Message for gamma interferon (IFN-gamma) was identified by light microscopy in 11 of the 12 granulomas, and interleukin-2 (IL-2) message was identified in 9 of the 12. By laser scanning confocal microscopy, significantly increased IFN-gamma and IL-2 pixel intensity was identified in nearly all of the granulomas from early histologic stages. Message for IL-4 was seen in 6 of the 12 granulomas. Only granulomas with complete destruction of the parasite architecture displayed more than minimal amounts of IL-4 message by light microscopy, and only 2 of 12 granulomas had IL-4 pixel intensity significantly above background. Only minimal amounts of IL-10 message were detected in 4 of 11 granulomas. Thus, early granulomas in cysticercosis are predominantly associated with a Th1 response, whereas later granulomas, in which parasite destruction is complete, have a mixture of Th1 and IL-4. The Th1 response appears to play an important role both in the pathogenesis of disease as well as in the clearing of the parasites, with IL-4 involved in downregulation of the initial response.

Animals↗

In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas.

Human tuberculous granulomas from five adults undergoing surgery for hemoptysis were analyzed by nonradioactive in situ hybridization for tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), and interleukin-4 (IL-4) gene expression. All of the patients produced TNF-alpha mRNA. Three patients stained positive for both IFN-gamma and IL-4 mRNA; the other two stained positive for IFN-gamma but not IL-4 mRNA. Heterogeneity between the granulomas was observed in those patients staining positive for both IFN-gamma and IL-4 mRNA; these patients exhibited granulomas having IFN-gamma and not IL-4 mRNA as well as granulomas positive for both cytokine mRNAs. There was no evidence of caseation in these granulomas, and the cytokine patterns may represent events in the evolution of the granuloma. However, in those granulomas exhibiting caseous necrosis, very little IFN-gamma or IL-4 mRNA was observed, implying that progression of the granuloma is accompanied by a down regulation of T-cell responses. TNF-alpha mRNA expression was highest in patients with both IFN-gamma and IL-4 mRNA. Populations of CD68 positive macrophage-like cells within the granulomas produce mRNA for TNF-alpha, IFN-gamma, and IL-4. This implies that macrophages within the tuberculous granuloma may not be dependent on T-cell cytokines for modulation of their function but may be able to regulate their own activation state and that of the surrounding T cells. These findings have implications on the delivery of immunotherapies to patients with tuberculosis.

Adult↗

Clinicoradiological and pathological correlations in patients with solitary cysticercus granuloma and epilepsy: focus on presence of the parasite and oedema formation.

A study of the clinical, radiological, and pathological correlations in 43 patients with solitary cysticercus granuloma and epilepsy focused on factors that might help in predicting the presence of the parasite in the granuloma and those that might influence the formation of oedema around the granuloma. The duration of symptoms (< six months and > or = six months) and CT morphology of the granuloma (ring and disc, type A; nodular lesion, type B) were studied as factors that could possibly predict the presence of the parasite in the granuloma. The influence of sex of the patient and the presence of a neutrophilic response in the granuloma on the intensity of oedema around the lesion as seen on CT was also studied. The pathological features were studied in the excised granulomas. The intact or degenerated form of the cysticercus was evident in 22 of 43 specimens. Neither the duration of seizures (P = 0.17) nor the type of lesion on CT (P = 0.16) was predictive of the presence of the parasite in the granuloma. The sex of the patient (P = 0.51) and the neutrophilic response in the specimen (P = 0.73) did not correlate with the degree of oedema on CT indicating that neither of these host factors was a major determinant of oedema production. The findings point to the varied and unpredictable natural history of solitary cysticercus granulomas and the complex nature of host-parasite interactions in individual patients. The inability to predict the presence of the parasite in the granuloma on the basis of the clinical or radiological features precludes a selection of patients with such lesions for cysticidal drug treatment.

Adolescent↗

Quantitative comparison of infected Schistosomiasis mansoni and Haematobium: animal model analysis of the granuloma cell population.

To evaluate the hypothesis that the granuloma cell population in S. haematobium is different from that of S. mansoni infections, a hamaster animal model was established. Infection of hamesters was induced by abdominal skin exposure of male golden hamsters with 300 cercariae. S. haematobium granuloma cell population in the small intestine, urinary bladder, liver and spleen and those of S. mansoni granuloma in the small intestine and liver of infected hamsters were histologically examined between 6 and 12 weeks post-exposure. In both species, the granuloma cell population was fomed of lymphocytes (47%), histiocytes (28%), eosinophils (16%) and polymorphs (8%). As compared to granuloma cell population in S. haematobium; S. mansoni granulomas had: (a) higher population of eosinophils (28% vs. 11%), (b) lower population of polymorphs (4% vs. 10%) and histiocytes (22% vs. 31%) and (c) similar population of lymphocytes (46% vs.47%). The mean diameter of liver granuloma was higher in S. mansoni (175.8 +/- 12.34) than for S. haematobium (125.4 +/- 16.12). As compared to S. haematobium, the numbers of isolated male, female and total worms were significantly higher in S. mansoni (24.5 +/- 2.7 vs. 7.3 +/- 2.3; 6.3 +/- 0.8 vs. 2.2 +/- 0.5; 80 +/- 2.2 vs. 56.3 +/- 3.8, p < .0.05). The heterogeneity of cell population in granuloma suggests the involvement of different immune mechanisms in their development. The cells achieving numerical dominance in the granulomas were in the following order: lymphoyctes > monocytes > eosinophils > polymorphs. The differrence in the granuloma cell population between S. haematobium and S. mansoni may reflect different tissue reactions to the deposited ova.

Animals↗

In vitro studies on dermal granulomas of human leprosy: characterization of cells using monoclonal antibodies.

Single cell suspensions from granulomas of leprosy cases were prepared to enable an in vitro study on the characteristics of infiltrating cells. In all, biopsies from 21 untreated cases of tuberculoid leprosy and lepromatous leprosy were analyzed. The granulomas were found to contain lymphocytes and macrophages. The numbers of lymphocytes were higher in the suspensions of tuberculoid granulomas in comparison to lepromatous granulomas. A high percentage of lymphocytes from tuberculoid granulomas expressed OKT11 and Ia-like antigens, thereby indicating the presence of activated T cells. The proportion of Leu3a+ cells was greater in comparison to OKT8+ cells in these granulomas. In lepromatous granulomas, only a few positive lymphocytes expressing OKT11 or OKT8 antigens were observed. The ratio of Leu3a+:OKT8+ cells (2.79 +/- 0.61) was higher in the tuberculoid granulomas than in the lepromatous granulomas. Most macrophages from both types of granulomas expressed Ia-like antigens.

Antibodies, Monoclonal↗

Evolution of foam cells in subcutaneous rabbit carrageenan granulomas. II. Tissue and macrophage lipid composition.

This study describes the lipid composition of differentiating macrophage-derived foam cells in the inflammatory carrageenan granuloma. In this model, macrophages exposed in vivo to diet-induced hypercholesterolemia progressively accumulate electron-translucent lipid inclusions; and at 14 and 28 days, many assume the morphologic features of arterial plaque foam cells. Subcutaneous carrageenan granulomas were induced in 24 pellet-fed (NC) and 24 cholesterol-fed (HC) rabbits, and tissue was harvested at 4, 14, and 28 days. Total (TC) and free cholesterol (FC), cholesteryl esters (CEs), CE fatty acids, triglycerides (TGs), and phospholipids (PLs) were measured on lipid extracts from tissue. TC, FC, and CEs were also measured on isolated, cultured granuloma macrophages. Tissue TCs and FCs were significantly elevated in HC relative to NC rabbits at both 14 and 28 days (P less than 0.005 and P less than 0.01, respectively). CE accumulation in HC granuloma tissue was 80-fold greater at 14 days and 178-fold greater at 28 days (P less than 0.005), compared with NC granulomas. Oleic acid (18:1), the principal CE fatty acid in both NC and HC granulomas, accounted for significantly more (P less than 0.05) of the total CE fatty acids in HC (48%) relative to NC granulomas (37%). No net accumulation of TG was observed with time in NC or HC animals. Although diet did not influence tissue PL content, significant increases (P less than 0.05) were observed at 14 days in NC rabbits and at 14 and 28 days in HC rabbits relative to 4-day levels. CE accumulation was significantly greater in cultured macrophages isolated from HC granulomas at 14 days (P less than 0.001) and 28 days (P less than 0.01). These findings have demonstrated the significant accumulation of CEs in both HC granuloma tissue and in cultured HC macrophage/foam cells in vivo. The carrageenan granuloma model has, we believe, considerable potential for defining mechanisms responsible for CE accumulation in the differentiating macrophage-derived foam cell.

Animals↗

Organ-dependent differences in composition and function observed in hepatic and intestinal granulomas isolated from mice with Schistosomiasis mansoni.

In murine schistosomiasis mansoni, eggs deposited in the liver and intestines induce a cell-mediated granulomatous reaction. Previous studies have shown that maximal granuloma size differs in the liver and various segments of the gastrointestinal tract. The objective of this investigation was to isolate intestinal granulomas and to determine whether organ-dependent differences in cell composition and granuloma function exist. Intestinal granulomas representative of those in tissue were isolated by a combination of chemical and mechanical techniques. When dissociated by collagenase, these lesions yielded a viable heterogeneous population of inflammatory cells. Granulomas from the liver, colon, and ileum showed differences in cellular composition. Liver lesions contained the largest number of T and B lymphocytes, eosinophils, and mast cells whereas ileal granulomas comprised mostly macrophages. Immunofluorescence studies on frozen tissue sections revealed that T and B lymphocytes also displayed different patterns of distribution within granulomas from different tissues. In contrast to isolated cultured liver granulomas that produced MIF-like substances, isolated colonic and ileal granulomas had weak or no MIF activity. It thus appears that granuloma formation in various organs is influenced by local factors that could affect the ultimate resolution of the lesions.

Animals↗

T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA.

Schistosomiasis mansoni is a disease characterized by liver and intestinal granulomas. Previous investigations in our laboratory showed that nylon wool-adherent CD4+ T lymphocytes isolated from murine hepatic schistosome granulomas express receptors for somatostatin 1-14. Moreover, somatostatin 1-14 substantially decreased IFN-gamma and IgG2a, but not IL-5 secretion by dispersed granuloma cells. This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes. Amplification of mRNA by reverse transcription PCR shows SSTR1, SSTR2, and SSTR3 mRNA in normal mouse brain and other tissues. Nevertheless, only the SSTR2 PCR product was amplified from granuloma cell RNA. The nucleotide sequence of the granuloma SSTR2 PCR product from inflammatory cells is identical to the CBA murine brain SSTR2 cDNA sequence. Granuloma-derived T cell lines, FACS-isolated granuloma CD4+ T cells, thymocytes, splenocytes, and cloned T cell lines all contain mRNA for SSTR2 by reverse transcription PCR. Moreover, both SSTR2A and the splice variant SSTR2B can be amplified from dispersed granuloma cells, granuloma T cell lines, thymocytes, and splenocytes. This is the first demonstration that inflammatory cells produce mRNA for an authentic somatostatin receptor. It is probable that the lymphocyte SSTR2 receptor mediates somatostatin-induced modulation of IFN-gamma secretion.

Animals↗

IL-2 contributes to the IL-5 response in granulomas from mice infected with Schistosoma mansoni.

Th cells within the granulomas of murine schistosomiasis mansoni produce IL-5, which is essential for granuloma eosinophil growth and development. The mechanisms regulating granuloma IL-5 production are unknown. The granulomas also make IL-2 in small quantities. rIL-2 therapy stimulates eosinophilia and IL-5 synthesis. Therefore, we studied the effect of IL-2 on IL-5 production within the liver granulomas of murine Schistosoma mansoni. Dispersed granuloma cells and intact granulomas cultured in vitro released IL-5. Adding anti-IL-2 or anti-IL-2R to the cultures, to block IL-2 activity, significantly inhibited IL-5 production. However, supplementing the cultures with small quantities of rIL-2 markedly stimulated IL-5 release in a dose-dependent fashion. Blocking anti-IL-4 mAb had no effect. Also, granuloma T cells were isolated by FACS. These highly purified T cells produced IL-5 both in the presence and absence of plate-bound anti-CD3. Once again, the IL-5 production was dependent on IL-2. The requirement of IL-2 for normal IL-5 production was not dependent on an IL-2-induced expansion of the IL-5-producing, T lymphocyte population. Thus, IL-2 mediates T cell interactions within the granuloma that regulate granuloma IL-5 secretion.

Animals↗

[Granuloma of the pancreas].

1. Granulomas in the pancreas are not equivalent to granulomatous pancreatitis. 2. Apart from foreign body granulomas on the pseudocyst margin (endogenous foreign body), and around the past operation stitch rests (exogenous foreign body), we have found thirty-six cases of granulomas in 1000 cases of chronic pancreatitis. Occasionally one could find granulomas around Ethibloc residues. The frequency could not be exactly determined, because most of Ethibloc reacted parts of the glands were not operated (removed). 3. We could not clarify the etiology in 20 cases (so-called cryptogenous granulomas). There were 7 cases of vessel granulomas, partly with complete obliteration of the arteries: arteriitic granulomas. The granulomas were always found in many arteries of the same caliber, never in solitary vessels. These findings were always preceded by arteriography. 4. Granulomatous pancreatitis was organ manifestation in primary Syphilis (2 cases) and primary M. Boeck (2 cases). We found fungal granulomas in AIDS. 5. Granulomatous pancreatitis plays a subordinate role in the complete picture of the basic disease; but it can cause an obstructive icterus and show a tumoral symptom.

Arteritis↗