vasoactive-intestinal-peptide and Staphylococcal-Infections

The vaginal epithelium provides a barrier to pathogens and recruits immune defenses through the secretion of cytokines and chemokines. Several studies have shown that mucosal sites are innervated by norepinephrine-containing nerve fibers. Here we report that norepinephrine potentiates the proinflammatory response of human vaginal epithelial cells to products produced by Staphylococcus aureus, a pathogen that causes menstrual toxic shock syndrome. The cells exhibit immunoreactivity for catecholamine synthesis enzymes and the norepinephrine transporter. Moreover, the cells secrete norepinephrine and dopamine at low concentrations. These results indicate that norepinephrine may serve as an autocrine modulator of proinflammatory responses in the vaginal epithelium.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Cell Line, Transformed; Dopamine; Epithelial Cells; Female; Humans; Immunomodulation; Interleukin-6; Interleukin-8; Neuroimmunomodulation; Neuropeptide Y; Norepinephrine; Peptide Fragments; Phentolamine; Propranolol; Shock, Septic; Staphylococcal Infections; Superantigens; Vagina; Vasoactive Intestinal Peptide

We have previously shown that inhibition of the proinflammatory cytokine tumor necrosis factor- (TNF)-alpha exacerbates the inflammatory process of EIU. To further examine this paradoxic phenomenon, we investigated here the effect on EIU of VIP, a neuropeptide that inbibits TNF-alpha production.. VIP was injected concurrently with endotoxin at doses that induce EIU or lethality in mice. Severity of EIU was measured by counting infiltrating cells in eye sections, at 1 or 5 days post endotoxin injection. Survival of mice was monitored periodically, while serum levels of TNF-alpha, interleukin-(IL)-1beta and IL-10 were determined by caputure ELISA.. Treatment with VIP exacerbated EIU but provided partial protection from the lethal endotoxin effect. VIP treatment also reduced serum levels of TNF-alpha and IL-1beta, but increased levels of IL-10.. This study further established the paradoxical observation that EIU is exacerbated by lowering the levels of circulating pro-inflammatory cytokines, in particular TNF-alpha.

Topics: Animals; Anterior Eye Segment; Endotoxemia; Endotoxins; Enzyme-Linked Immunosorbent Assay; Interleukin-1; Interleukin-10; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Staphylococcal Infections; Staphylococcus; Tumor Necrosis Factor-alpha; Uveitis, Anterior; Vasoactive Intestinal Peptide