In vivo study of histamine H4 receptor in immunomodulation

Objective: Recently accumulating evidence has highlighted the role of histamine in inflammation and immune reaction by histamine H4-receptor, however the role of histamine via H4-receptor in immunomodulation is still unclear. Therefore, the present study was designed to study the immunomodulatory role of histamine H4-receptor on antibody generation profile in rabbit. Methods: The cohort study comprised of 108 rabbits in six groups. Each group consisted of 18 rabbits. Group I (negative control) remained non-immunized and received vehicle (sterile distilled water, 1 mlkg(-1) x b.i.d., s.c. for 10 days (3 days prior to immunization until 7 days after immunization)). Group II (positive control) received vehicle (1 mlkg(-1) x b.i.d., s.c. for 10 day), while group III-VI received histamine (100 mu gkg(-1) x b.i.d., s.c.), H4-agonist (clobenpropit dihydrobromide, 10 mu gkg(-1) x b.i.d., s.c.), and H4-antagonist (JNJ 7777120, 10 mu gkg(-1) x bid., i.m.) and DMSO (control group for H4R-antagonist, 1 mlkg(-1) x b.i.d., i.m.) respectively for 10 days. Group II-VI were immunized with intravenous injection of sheep red blood cells (SRBC) on day 3. Immunological parameters [immunoglobulins (Ig), immunoglobulin M (IgM), and immunoglobulin G (IgG)] assessed by the whole SRBC-ELISA method and direct hemagglutination assay. Results: Histamine could influence a detectable antibody response to SRBC as early as day 7 postimmunization (post-I), which lasted until day 58 post-I, whereas H4-receptor by H4R-antagonist treatment showed a similar profile of antibody (Ig, IgM, and IgG) generation as the positive control group. On the other hand, H4R-agonist treatment showed immunostimulant activity as compared to other experimental groups. The results were found statistically significant (p < 0.01). Conclusions: Histamine H4-receptor in biological system modulates immunological function and stimulates antibody production only by exogenously administered agonists not by endogenous histamine (Tab. 1, Fig. 3, Ref. 26). Full Text in PDF www.elis.sk.