Lateralization and catecholaminergic neuroimmunomodulation: Prazosin, an a1/a2-adrenergic receptor antagonist, suppresses interleukin-1 and increases interleukin-10 production induced by lipopolysaccharides

Objective: The brain has previously been shown to asymmetrically modulate neurochemical, neuroendocrine and immune responses to lipopolysaccharides (LPS). As these responses are reversed by a chemical sympathectomy, it can be hypothesized that the asymmetry in the functioning of the sympathetic nervous system may be one of the mechanisms by which the brain hemispheres asymmetrically modulate immune reactivity. Methods: The effects of prazosin, an alpha1/alpha2-adrenergic receptor antagonist, on the production of interleukin (IL)1beta and IL-10 induced by LPS was studied in mice selected for their paw preference. Results: Two hours after intraperitoneal injection of 5 mug of LPS, plasma levels of IL-1beta were higher in right-pawed mice as compared to left-pawed or ambidextrous animals. No lateralization effect was observed for LPS-induced plasma IL-10 levels. Prazosin, 10 mg/kg, injected intraperitoneally half an hour before LPS, reduced plasma levels of IL-1beta and abolished the effect of lateralization. By contrast, prazosin drastically increased plasma levels of IL-10 in response to LPS and the production of corticosterone in untreated controls. Conclusions: These results suggest that the catecholaminergic modulation of immune reactivity depends on lateralization. This work further demonstrates that prazosin is endowed with anti-inflammatory properties that may be considered side effects of this drug, which is widely prescribed in the treatment of hypertension. Copyright (C) 2002 S. Karger AG, Basel.