In vivo study of histamine H4 receptor in immunomodulation.

Abstract 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 × 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 × b.i.d., s.c. for 10 day), while group III-VI received histamine (100 µgkg-1 × b.i.d., s.c.), H4-agonist (clobenpropit dihydrobromide, 10 µgkg-1 × b.i.d., s.c.), and H4-antagonist (JNJ 7777120, 10 µgkg-1 × b.i.d., i.m.) and DMSO (control group for H4R-antagonist, 1 mlkg-1 × 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). Keywords: histamine receptors, immunomodulation, T-cell dependent antibody response, humoral immune response, H4-antagonist, H4-agonist, Rabbit, Sheep red blood cells.