Effect of a Synthetic Immunomodulator on the Regulation of Gamma Interferon and Interleukin-10 Production during Salmonella Sepsis in Ity s Mice

Abstract

The present study examined the in vivo capacity of diHDA-glycerol, a new chemically defined compound that we synthesized, to enhance nonspecific resistance of Ity^s mice to a virulent Salmonella typhimurium challenge (>LD50). This compound derives from (E)-10 hydroxy-2 decenoic acid (10-HDA), a fatty acid isolated from Royal Jelly. Bacterial growth rate within the spleen, interferon-gamma (IFN-γ), interleukin-10 (IL-10), and nitric oxide (NO) levels were measured in splenocyte cultures from diHDA-glycerol-pretreated mice or saline infected controls, at various time intervals after infectious challenge. Repeated administration of diHDA-glycerol before bacterial inoculation resulted in increased bacterial clearance from the spleen, starting in the second week of infection, whereas in control mice, bacterial proliferation led to death beyond day 13 after challenge. In addition, spleen cells from infected mice produced elevated levels of IFN-γ but failed to produce IL-10. In contrast, on the second week post challenge, the time course of cytokine responses was modified by the pretreatment. Spleen cells from diHDA-glycerol pretreated mice exhibited significantly lower levels of IFN-γ and significantlty higher levels of the anti-inflammatory cytokine IL-10, when compared with those in infected controls. Furthermore, on the second week post challenge, the restored functional capacity of splenocytes to produce nitric oxide (NO) was apparently linked with diHDA-glycerol pretreatment. These results suggest that diHDA-glycerol accelerates some macrophage functions resulting in a more adequate modulation of the balance of inflammatory mediators and consequently, in an enhanced host defense against Salmonella infection.