The involvement of prostaglandin E₂ in interleukin-1β evoked anorexia is strain dependent

From experiments in mice in which the prostaglandin E₂ (PGE₂) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE₂ was injected directly into the brain, PGE₂ has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE₂ receptor (EP_1-4) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP₁, EP₂, and EP₃) or selectively in the nervous system (EP₄), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE₂ in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE₂ in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice.