Santosh Khanna

Immunomodulation Due to Coexposure to Styrene and Dioctyl Phthalate in Mice

Pathomorphological and immunological alterations caused by a mixture of styrene and dioctyl phthalate were studied in albino mice following oral administration of 0.02, 0.03, 0.05 x LD50 of the mixture. The chemicals were mixed together proportionate to their respective LD50 values and fed in ground nut oil, 5 d/wk for 4 weeks. Histological examination of spleen revealed considerable depletion of cellular population of lymphoid follicles which corresponded to the dose dependent decrease in splenic mononuclear cell population count. The thymic lobules revealed slight atrophy but accompanied by a significant increase in thymocyte population. Correspondingly few significant histological changes were observed in mesenteric and peripheral lymph nodes. The treatment caused impairment of primary humoral immune response to SRBC (IgM) but there was a significant increase in response of splenocytes to B-cell mitogen LPS. There was a suppression of cutaneous delayed type hypersensitivity and increase in splenic lymphocyte response to T-cell mitogen PHA. Simultaneously, indirect immunity represented by decreased phagocytosis and enhanced metabolic function of reducing NBT by peritoneal exudate cells was observed. The in vitro exposure of vero cells to the mixture caused dose dependent protective effect. The results of present study indicate that subchronic exposure to low doses of mixture of styrene and dioctyl phthalate under certain conditions may modulate some of the immune functions as compared to exposure to either chemicals alone.

Dibutyltin Dilaurate Induced Thymic Atrophy and Modulation of Phosphoinositide Pathway of Cell Signalling in Thymocytes of Rats

A marked dose dependent reduction in thymus weight and its nucleated cell counts with histological alterations was observed in rats exposed to oral dibutyltin dilaurate (DBTL) for 2 weeks at 2, 4, 8 or 16 mg/kg body weight. The incorporation of [3H]-inositol into all the three major phosphoinositides was drastically reduced in thymocytes in a dose dependent manner. Furthermore, the basal and the mitogen (Con A) stimulated [3H]-inositol phosphates generation was diminished significantly in 8 mg DBTL group. However, in vitro incubation of DBTL with thymocytes failed to evoke any change in phosphoinositide hydrolysis. Similarly, a time and dose dependent inhibition in phosphoinositide synthesis with as high as 80% by 10 microM DBTL was exhibited under in vitro conditions. A 130% and 600% enhancement of protein kinase C (PKC) activity in thymocytes was seen in 4 mg and 8 mg DBTL group, respectively. Addition of DBTL to the cell free assay system of thymocytes resulted in a concentration dependent activation of the enzyme activity. A dose dependent increase in intracellular calcium was also evident when DBTL was added to thymocytes under in vitro conditions. These results are of significance and may bear close relationship to the observed thymic atrophy by DBTL.