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PubMed1977

[Role of antigens and adjuvant substances in the histological response in experimental granulomas (immunogenic granuloma)].

The injection in rabbits of vaccinal antigens combined with immunity adjuvants (in particular calcium phosphate) causes a local lesion in which it is possible to recognize histologically, after a transitory afflux of polymorphonuclear leukocytes, a central area of adjuvant deposit, a middle area of histiocytes and monocytes, and a peripheral immunogenic area of lymphocytes and plasmocytes. These two cellular zones are rich in highly fluorescent cells in the presence of an antiglobulin serum with an embedding technique which respects to the upmost the structures and immunoreactivity of the cells. These histological features are not completely observed on the separate injection of antigen or adjuvant. They must be interpreted, after a fleeting non-specific reaction, while taking into account the still poorly understood method of action of the inorganic adjuvant and spread of the antigen in the organism.

Adjuvants, Immunologic↗
PubMedDate not supplied

The prevalence of hepatic granulomas in chronic hepatitis C.

OBJECTIVES: Hepatic granulomas are not usual findings in chronic hepatitis C. A few studies addressing the frequency of hepatic granulomas in chronic hepatitis C reported it as less than 10%. The presence of it has been suggested to predict a favorable response to interferon treatment. Also, case reports described the development of hepatic granulomas after interferon treatment. In this study, we aimed to detect the prevalence of hepatic granulomas in chronic hepatitis C and to identify the causes other than chronic hepatitis C, if present, to search whether there is an association between the presence of granuloma and response to interferon treatment and also to see whether interferon leads to the formation of hepatic granulomas. METHODS: Patients from 3 university clinics were included. All patients with chronic hepatitis C were determined. All patients with hepatic granulomas were screened for the other causes of hepatic granuloma with tuberculin skin test, chest X-ray and computed tomography, Venereal Disease Research Laboratory, and Brucella agglutination tests. The histologic assessment of liver biopsies was done by the same pathologist in each center. RESULTS: A total of 725 liver biopsies of 605 patients with chronic hepatitis C were screened. In 8 patients, hepatic granulomas were detected in the initial liver biopsies. Four patients had repeat biopsies, and all had hepatic granulomas again. The prevalence of hepatic granulomas in patients with chronic hepatitis C was calculated as 1.3% (8 of 605) in reference to patient population. Presence or absence of hepatic granulomas was seemingly stable. All patients with hepatic granulomas had negative results of tuberculin skin test, Venereal Disease Research Laboratory, chest X-ray and computed tomography, and Brucella agglutination tests. All repeat biopsies were obtained after interferon (+/- ribavirin) in varying doses and duration. Four of 8 patients with hepatic granulomas were found to respond interferon therapy. No patient was found to develop hepatic granulomas after interferon therapy. CONCLUSION: Hepatic granulomas are a rare finding in HCV infection. The presence of it does not seem to predict the response to interferon therapy. The development of hepatic granulomas during interferon therapy is not usual.

Biopsy↗
PubMed2002

Sequential expression of the neuropeptides substance P and somatostatin in granulomas associated with murine cysticercosis.

Neurocysticercosis, a parasitic infection of the human central nervous system caused by Taenia solium, is a leading cause of seizures. Seizures associated with neurocysticercosis are caused mainly by the host inflammatory responses to dying parasites in the brain parenchyma. We previously demonstrated sequential expression of Th1 cytokines in early-stage granulomas, followed by expression of Th2 cytokines in later-stage granulomas in murine cysticercosis. However, the mechanism leading to this shift in cytokine response in the granulomas is unknown. Neuropeptides modulate cytokine responses and granuloma formation in murine schistosomiasis. Substance P (SP) induces Th1 cytokine expression and granuloma formation, whereas somatostatin inhibits the granulomatous response. We hypothesized that neuropeptides might play a role in regulation of the granulomatous response in cysticercosis. To test this hypothesis, we compared expression of SP and expression of somatostatin in murine cysticercal granulomas by using in situ hybridization and immunohistochemistry. We also compared expression with granuloma stage. Expression of SP mRNA was more frequent in the early-stage granulomas than in the late-stage granulomas (34 of 35 early-stage granulomas versus 1 of 13 late-stage granulomas). By contrast, somatostatin was expressed primarily in later-stage granulomas (13 of 14 late-stage granulomas versus 2 of 35 early-stage granulomas). The median light microscope grade of SP mRNA expression in the early-stage granulomas was significantly higher than that in the late-stage granulomas (P = 0.008, as determined by the Wilcoxon signed rank test). By contrast, somatostatin mRNA expression was higher at later stages (P = 0.008, as determined by the Wilcoxon signed rank test). SP and somatostatin are therefore temporally expressed in granulomas associated with murine cysticercosis, which may be related to differential expression of Th1 and Th2 cytokines.

Animals↗
PubMed1998

Intraoperative cytologic diagnosis of granulomas: a retrospective study of 156 cases.

To avoid contamination of equipment and reduce risks of infection, intraoperative cytology (IOC) is a useful substitute to conventional frozen section in the diagnosis of infectious diseases. One of the various histomorphologic patterns of infections is the granuloma, which sometimes may be difficult to diagnose cytologically. In an attempt to assess accuracy and pitfalls of IOC in the diagnosis of granuloma, cases diagnosed as granuloma on IOC or on permanent sections (PS) at George Washington University Medical Center were collected for the period of September 1990 to March 1996. Cyto-histologic correlation was performed. During that time, a diagnosis of granuloma in either the IOC or PS was rendered in 156 of 5,901 IOC cases. IOC showed definite granuloma (87), suspicious for granuloma (23), and neither definite nor suspicious for granuloma in 46 cases. The latter group corresponded to neoplasms (5) and benign conditions (41). Eighty-five cases were accurately diagnosed as definite granuloma by both IOC and PS. Fifty-seven cases diagnosed as granuloma by PS corresponded on IOC to suspicious for granuloma (11), benign smear (41), and neoplasms (5). Only two cases were incorrectly diagnosed as granuloma on IOC: a neoplasm and a case of fibrosis. Overall, four cases of neoplasms were interpreted as suspicious for granuloma (3) or definite granuloma (1) on IOC, and five cases of granulomas were misdiagnosed as neoplasms on IOC. Four of these nine case were deferred for a PS diagnosis. IOC is a useful tool in the diagnosis of granulomas with a sensitivity of 60% and specificity of 99% and positive and negative predictive values of 98% and 99%, respectively. Rarely, neoplasms may be misdiagnosed as granulomas and vice versa.

Adult↗
PubMed2002

Th2-type granuloma development in acute murine schistosomiasis is only partly dependent on CD4+ T cells as the source of IL-4.

Schistosome granulomas produce IL-4, important for Th2 granuloma expression. We defined the origins of IL-4 within these granulomas and the role of IL-4-producing CD4(+) T cells in Th2 granuloma development. Dispersed granuloma cells spontaneously produced IL-4 independently of T cells, whereas IL-5 production was T cell dependent. Granuloma IL-4 mRNA localized to the non-T cells and IL-5 to T cells. Granuloma CD4(+) T and NK cells, but not B cells produced IL-4 and IL-5 in vitro. B cell-/- mice generated Th2 granulomas that produced IL-4 and IL-5 normally. Granuloma eosinophils expressed no IL-4 or IL-5 mRNA. Granulomas in WWv mast cell-deficient mice lacked mast cells. The dispersed granuloma cells from WWv mice released IL-4 only after T cell stimulation, suggesting that mast cells influenced the constitutive component of IL-4 production. Rag-1 animals (T/B/NK T cell deficient) given schistosomiasis after reconstitution with splenocytes from naive mice produced Th2 granulomas. Mice reconstituted to create selective CD4(+) T cell IL-4 knockout animals developed eosinophilic granulomas that made IL-4. Thus, granulomas contain several cell types that produce IL-4. Mast cells are not needed to form Th2 granulomas, but influence IL-4 release. Th2 granuloma development in schistosomiasis is only partly dependent on IL-4-producing CD4(+) T cells.

Animals↗