Gonadotropin-releasing hormone agonist prevents l-arginine induced immune dysfunction independent of gonadal steroids: Relates with a decline in elevated thymus and brain nitric oxide levels

• We examined the dose related toxicity of l-arginine on immune responses, thymus morphology and its DNA integrity.
• We evaluate the brain and thymus nitrites levels to correlate with the impaired immune parameters.
• Leuprolide, a GnRH agonist prevents the l-arginine induced immunotoxity, and attenuates brain and thymus nitrites levels.
• We used intact, castrated, and ovariectomized mice to know sex hormones influence.
• Leuprolide eliminates immune toxicity induced by l-arginine; unrelated to its gonadal interaction.

The present study was carried out to find out the effect of leuprolide, a gonadotropin-releasing hormone (GnRH) receptor agonist, on l-arginine induced immunosuppression, and relates with brain and thymus levels of nitric oxide (NO). Further, the effect of leuprolide was studied in sham operated, ovariectomized and castrated mice to understand the role of sex steroids in l-arginine induced immunosuppression. Treatment with l-arginine (250, 500, 1000 mg/kg/i.p. for 7 days) increased brain and thymus levels of NO; measured by using ‘NO Measuring Instrument’ (Innovative Instruments Inc., USA) in dose dependent manner. It also decreased cellularity, relative weight of thymus, DNA fragmentation, humoral, and cell mediated immunity response to sheep RBC.Prior treatment of leuprolide (100μg/mouse, s.c. for 7 days) prevented l-arginine induced rise in brain and thymus tissue levels of NO as well as the changes in immunological parameters. The protective effect of leuprolide against l-arginine induced immunosuppression and rise in brain and tissue nitric oxide levels was even evident in ovariectomized and castrated mice, suggesting that the observed effect of leuprolide is independent of sex steroids, and correlated with its ability to prevent l-arginine induced rise in CNS and peripheral immune tissue levels of NO.