Immunohistochemical study of inducible nitric oxide synthase [iNOS] in peritoneal Tuberculous granuloma

Nitric Oxide [NO] is important in host defense against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. This study aimed to investigate iNOS expression by peritoneal macrophages in TB peritonitis and to gain insights into the structural properties of peritoneal TB granuloma. Peritoneal biopsies were obtained from 28 undiagnosed cases of ascites and examined histopathologically by H and E stain. Accordingly, specimens proved to be TB peritonitis were then immunohistochemically stained for iNOS, the macrophage marker CD68 and CD3 and CD20 as markers of T and B lymphocytes respectively. Eight control cases of normal peritoneum were included. TB peritonitis was diagnosed in 16 cases. TB granulomas were found in 9/16 cases [56%] and a diffuse granulomatous reaction was found in the remaining7/16 cases [44%]. Immunoreactivity to iNOS and CD68 were intensely expressed in macrophage rich TB granuloma and in the diffuse granulomatous TB reaction. Most Langhans cells [multinucleated giant cells] showed strong reactivity to both CD68 and iNOS. In TB granuloma, CD3[+] cells were found at the periphery with few CD20[4] cells in its center. Control cases showed complete negativity for iNOS, CDS, very small number of CD68 and/or CD20 cells. In TB peritonitis, an increased local expression of iNOS in granuloma associated macrophages of untreated patients indicating excess NO production in the active stage of this form of Tuberculosis. Further studies are needed to test the therapeutic implications of NO in different forms of TB

Immunohistochemical study of INOS in peritoneal tuberculous granuloma

The human tuberculous granuloma provides the morphological basis for local immune processes central to the outcome of tuberculosis. Nitric Oxide [NO], produced by the inducible nitric oxide synthase [INOS], is important in host defense against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. Because of the scarcity of information in human patients especially in peritoneal tuberculosis, the present study aimed to: 1-investigate iNOS expression by peritoneal macrophages in TB peritonitis. 2- gain insights into the structural properties of peritoneal TB gronuloma. Laparoscoy was done for 28 patients with undiagnosed ascites and peritoneal biopsies were obtained and examined histopathologically by H and E stain. Accordingly, specimens proved to be TB peritonitis were then iminunohistochemically stained for iNOS, the macrophage marker CD 68 and CD 3 and CD 20 as markers of T and B lymphocytes respectively. Eight Control cases of peritoneum removed with surgically excised organ specimens [e.g. with excised tumors] were included. TB peritonitis was diagnosed in 16 cases. TB granulomas were found in 9/16 cases [56%] and a diffuse granulomatous reaction was found in the remaining 7/16 cases [44%]. Immunoreactivity to iNOS and the macrophage marker CD 68 were intensely expressed in macrophage rich TB granuloma and in the diffuse granulomatous TB reaction. Most Langhans cells [multinucleated giant cells] showed strong reactivity to both CD 68 and iNOS. The expression intensity of iNOS and/or CD 68 was stronger in diffuse and premature-stage granulomas than in late-stage granulomas [caseating granuloma]. In TB granuloma, CD 3 cells were found at the periphery with few CD 20[+] cells in its center. While in diffuse granulomatous TB reaction, CD 3[+] lymphocytes were diffusely dispersed in the lesion with few CD 20[+] lymphocytes. Control cases showed complete negativity for iNOS, CD 3, very small number of CD 68 and/or CD 20 cells. In TB peritonitis, the distribution of different immune cells in the granuloma is similar to that described in pulmonary TB granulomas. An increased local expression of iNOS in granulomas associated macrophages of untreated patients indicating excess NO production in the active stage of this form of Tuberculosis. Further studies are needed to test the therapeutic implications of NO in different forms of TB

Relation of leptin and proinflammatory cytokines to anorexia and wasting in pulmonary and extrapulmonary tuberculosis

Tuberculosis is the classic cause of "consumption," but the exact pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between pro inflammatory cytokine activity and wasting. Because leptin is involved in weight regulation and cellular immunity, it may have a role in tuberculosis-associated wasting. Qims: 1] To estimate leptin concentration in a group of active pulmonary or extra pulmonary tuberculosis as compared to healthy control subjects. 2] To study the relationship between serum leptin, anorexia and wasting. 3] To study the correlation between serum leptin and proinflammatory cytokines [TNF-d, IL-1,IL-6] Patients and Non-diabetic Egyptian adults with pulmonary [n=26] and extrapulmonary tuberculosis [n=19] as well as 20 healthy controls were recruited into a case-control study. Body mass index [BMI], C- reactive protein, serum leptin, TNF-a, interleukin-1 and 6 were measured. According to the calculated BMI, eighteen patients were wasted [40%] and 27 [60%] were not wasted. Mean serum leptin was significantly lower in tuberculous patients than controls and in wasted than non-wasted patients. TNF-a, IL-l.IL-6 were significantly higher in patients than controls. Only IL-6 was significantly higher in wasted than non-wasted patients Serum leptin showed a significant positive correlation with BMI. While, IL-6 had a significant negative correlation with BMI Moreover, stepwise linear regression analyses showed that IL-6 was the only factor significantly contributing to loss of appetite [anorexia] in tuberculous patients. leptin does not appear to be part of the proinflammatory cytokine response in human tuberculosis. Changes in leptin are entirely appropriate for the changes in body mass index. Altered leptin activity cannot, therefore, be held responsible for the weight loss and anorexia so often associated with tuberculosis infection. Anorexia and wasting seem primarily determined by the level of inflammatory cytokine [IL-6]