title: 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).
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College & Hospital, Aligarh Muslim University, Aligarh, India.
authors.forename: T
authors.initials: T
authors.lastname: Tripathi
authors.forename: M
authors.initials: M
authors.lastname: Shahid
authors.forename: H M
authors.initials: HM
authors.lastname: Khan
authors.forename: M
authors.initials: M
authors.lastname: Siddiqui
authors.forename: R A
authors.initials: RA
authors.lastname: Khan
authors.forename: F
authors.initials: F
authors.lastname: Shujatullah
authors.forename: S
authors.initials: S
authors.lastname: Moin
authors.forename: A
authors.initials: A
authors.lastname: Malik
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006386:Hemagglutination Tests; D007093:Imidazoles / Q000494:pharmacology; D007114:Immunization; D007136:Immunoglobulins / Q000096:biosynthesis*; D008297:Male; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology*; D000074040:Receptors, Histamine H4; D012756:Sheep; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C418607:HRH4 protein, human; D007093:Imidazoles; D007136:Immunoglobulins; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D013890:Thiourea; C086108:clobenpropit