Inhibition of xanthine oxidase does not influence immunosuppression after hemorrhagic shock. 1997

G C Pinault, and A J Sanson, and M A Malangoni
Department of Surgery, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109-1998, USA.

BACKGROUND Resuscitated hemorrhagic shock causes global ischemia reperfusion with generation of toxic oxygen metabolites. We hypothesized that the immunosuppression that follows hemorrhagic shock may be linked to this process. METHODS Forty-five male Sprague-Dawley rats (weight, 250-300 g) were bled to a mean arterial pressure of 30 mm Hg for 60 minutes, then were resuscitated with three times the maximum blood loss of lactated Ringer's solution. Immune response was assessed by splenocyte proliferation and interleukin-2 (IL-2) production 72 hours after hemorrhage. Allopurinol (50 mg/kg) was given after hemorrhage and immediately before resuscitation. RESULTS Hemorrhagic shock caused significant decreases in splenocyte proliferation (cpm: (157,880 +/- 22,068 (mean +/- SD) vs. 37,787 +/- 15,849) and IL-2 production (1/2 max U/ml: 79.6 +/- 7.9 vs. 48.0 +/- 7.7) (both p < 0.05). Hepatic xanthine oxidase was significantly increased with hemorrhage and resuscitation. Hepatic xanthine oxidase activity after hemorrhage and resuscitation was significantly decreased after treatment with allopurinol (74.2 +/- 41.7 vs. 9.2 +/- 9.40). Allopurinol did not affect splenocyte proliferation (cpm: 21,875 +/- 9,316) or IL-2 production (1/2 max U/ml: 45.0 +/- 7.1). CONCLUSIONS These results demonstrate that inhibition of xanthine oxidase by allopurinol after hemorrhagic shock did not affect splenocyte proliferation or IL-2 production. We conclude that the immunosuppression after hemorrhagic shock is not dependent on xanthine oxidase-induced production of toxic oxygen metabolites.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008297 Male Males
D012151 Resuscitation The restoration to life or consciousness of one apparently dead. (Dorland, 27th ed) Resuscitations
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000493 Allopurinol A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms. Allohexal,Allohexan,Alloprin,Allopurin,Allorin,Allpargin,Allural,Apulonga,Apurin,Atisuril,Bleminol,Caplenal,Capurate,Cellidrin,Embarin,Foligan,Hamarin,Jenapurinol,Lopurin,Lysuron,Milurit,Milurite,Novopurol,Pan Quimica,Progout,Pureduct,Purinol,Remid,Rimapurinol,Roucol,Suspendol,Tipuric,Uribenz,Uridocid,Uripurinol,Urosin,Urtias,Xanthomax,Xanturic,Zygout,Zyloprim,Zyloric
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012771 Shock, Hemorrhagic Acute hemorrhage or excessive fluid loss resulting in HYPOVOLEMIA. Hemorrhagic Shock
D013154 Spleen An encapsulated lymphatic organ through which venous blood filters.

Related Publications

G C Pinault, and A J Sanson, and M A Malangoni
January 1994, Circulatory shock,
G C Pinault, and A J Sanson, and M A Malangoni
October 1997, Shock (Augusta, Ga.),
G C Pinault, and A J Sanson, and M A Malangoni
March 1991, Circulation,
G C Pinault, and A J Sanson, and M A Malangoni
September 1984, The Journal of biological chemistry,
G C Pinault, and A J Sanson, and M A Malangoni
May 1992, The Journal of trauma,
G C Pinault, and A J Sanson, and M A Malangoni
October 1993, Free radical biology & medicine,
G C Pinault, and A J Sanson, and M A Malangoni
January 1992, Basic research in cardiology,
G C Pinault, and A J Sanson, and M A Malangoni
January 2003, Shock (Augusta, Ga.),
Copied contents to your clipboard!