Dopexamine and cellular immune functions during systemic inflammation.
An immune-neuroendocrine interaction that is mediated via beta2-adrenergic receptors has been demonstrated previously. Dopexamine is a substance with strong beta2-adrenergic effects and is used in the treatment of critically ill patients. We therefore investigated the effect of dopexamine infusion on survival and cellular immune functions during systemic inflammation. Sepsis (CLP) was induced in male NMRI mice that received either 0.9% saline, dopexamine (0.05 mg/kg/hour ip, DPX), the selective beta2-adrenergic antagonist ICI 118.551 (0.5 mg/kg ip every 12 hours, ICI) or a combination of both drugs. 48 hours after onset of sepsis, survival rate, splenocyte apoptosis, splenocyte proliferation, splenocyte IL-2, IL-6 and IFN-gamma release, and leukocyte distribution were monitored. Dopexamine increased splenocyte apoptosis and normalized the distribution of circulating lymphocytes but did not affect sepsis-induced mortality. ICI 118.551 induced a dramatic increase of mortality paralleled by a decreased splenocyte proliferation and the strongest increase in splenocyte apoptosis. Co-administration of dopexamine abolished the ICI 118.551-induced alterations but this effect seemed to be mediated via a pathway other than adrenergic beta2-receptors. We conclude that dopexamine modulates cellular immune functions during systemic inflammation and that different receptor systems are involved in the mediation of this process. Furthermore, the immunomodulatory effect of beta2-adrenergic blockade was demonstrated.
Oberbeck
Reiner
R
Department of Trauma Surgery, University Hospital of Essen, Germany. reineroberbeck@hotmail.com
Schmitz
Daniel
D
Schüler
Mark
M
Wilsenack
Klaus
K
Schedlowski
Manfred
M
Exton
Michael
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D051379:Mice; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013534:Survival; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000276:immunology*
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; C046318:dopexamine; D004298:Dopamine