Effect of l-arginine on restraint stress induced modulation of immune responses in rats and mice

Abstract

The present study investigates the role of nitric oxide (NO) on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses in rats and mice. RS produced suppression of humoral immune response, i.e., anti-SRBC antibody titre (7.38±0.32 versus 4.13±0.30; mean±S.E.M., P<0.001). In case of cell-mediated immunity, in delayed type hypersensitivity (DTH) response the change in paw volume decreased from 0.069±0.003 mm (mean±S.E.M.) in control non-stressed group to 0.038±0.002 mm in the stressed group ( P<0.001) while percentage leucocyte migration inhibition (% LMI) decreased from 39.7±1.95 in control non-stressed animals to 15.2±1.07 in animals subjected to stress ( P<0.01). Pretreating the animals with an NO precursor, l-arginine (1000 mg kg −1, i.p.) antagonized the effect of RS on humoral (anti-SRBC antibody titre 6.50±0.27 versus 4.13±0.30, P<0.001) and cell-mediated (DTH response 0.066±0.002 mm versus 0.038±0.002 mm, P<0.001; % LMI 41.5±1.46 versus 15.2±1.07, P<0.01) immune responses. Administration of 7-nitroindazole (7-NI, 50 mg kg −1, i.p.), an inhibitor of neuronal NO synthase, alone further enhanced the immunosuppressive effect of RS (anti-SRBC antibody titre 2.75±0.25 versus 4.13±0.30, P<0.001; DTH response 0.019±0.002 mm versus 0.038±0.002 mm, P<0.001; % LMI 5.0±1.08 versus 15.2±1.07, P<0.01). However, when given before l-arginine treatment, 7-NI reversed the effect of the latter drug on stress-induced immunomodulation (anti-SRBC antibody titre 3.00±0.27 versus 6.5±0.27, P<0.001; DTH response 0.043±0.003 mm versus 0.066±0.002 mm, P<0.001; % LMI 12.0±0.93 versus 41.5±1.46, P<0.01). Unlike its effect on RS-induced immune responsiveness, l-arginine (250, 500, 1000 mg kg −1) when given for 5–7 days to naive non-stressed animals produced dose dependent suppression of both humoral (anti-SRBC antibody titre 6.4±0.32 versus 5.4±0.32, 4.0±0.27, 3.1±0.30, respectively) and cell-mediated (DTH 0.065±0.003 mm versus 0.064±0.004 mm, 0.039±0.003 mm, 0.020±0.002 mm, respectively and % LMI 37.52±1.58 versus 30.48±1.07, 28.18±1.22, 19.76±0.83, respectively) immune responses. 7-NI significantly blocked these immunosuppressive effects of l-arginine (anti-SRBC antibody titre 6.0±0.38 versus 3.1±0.030, P<0.001; DTH response 0.056±0.004 mm versus 0.020±0.002 mm, P<0.001; % LMI 34.76±1.31 versus 19.76±0.83, P<0.01). However, 7-NI when given to non-stressed animals failed to modulate immune responsiveness. Thus, NO appears to play an important role in RS-induced immunomodulation and these effects are different from its effect on immune responsiveness in non-stressed animals.