In vivo comparative immunotoxic study of histamine receptors (H1R, H2R, H3R and H4R)-agonist

Accumulating evidences have highlighted histamine and histamine receptors (HRs)-antagonists’ role in immunomodulation. However, the roles of HRs-agonists are still unclear. The present study was therefore designed to delineate the comparative immunotoxic roles of H1-H4-agonist on antibody generation profile in rabbit model. The cohort comprised of seven groups (Group-I negative control, group-II positive control and group-III-VII HRs-agonist-treated) containing 18 (9 male and 9 female) rabbits each. Group-I and group-II received vehicle (sterile distilled water, 1mlkg-1×b.i.d.) intramuscularly. Groups-III-VII (HRs-agonist-treated) received subcutaneous histamine (100µgkg-1) and H1-agonist (HTMT), H2-agonist (amthamine), H3-agonist (R-[-]-?-methylhistamine) and H4-agonist (clobenpropit) each in a dose of 10µgkg-1, respectively, b.i.d. for 10 days (starting from day 1). Groups-II-VII were subsequently immunized with intravenous injection of SRBC at day 3. The estimation of serum immunoglobulins (Ig), IgM and IgG were done by ELISA, and observed at day 0 (pre-immunization) and day 7, 14, 21, 28 and 58 (post-immunization). Results showed that histamine and HRs-agonist could influence a detectable antibody response to SRBC as early as day 7-postimmunization (post-I), which lasted until day 58- post-I. All the results were found statistically significant (p<0.05). To conclude, our results provide evidences that HTMT, amthamine and clobenpropit (H1-, H2- and H4-agonist, respectively) have important role in modulation of antibody generation by enhancing production level, in which HTMT have dominant role, while amthamine and clobenpropit play similar role. Conversely, R-[-]-?-methylhistamine (H3-agonist) have dominant inhibitory role on antibody production.