Interleukin-10 modulates the synthesis of inflammatory mediators in the sensory circumventricular organs: Implications for the regulation of fever and sickness behaviors

Background: whereas the role played by interleukin (il)-10 in modulating fever and sickness behavior has been linked to it targeting the production of pro-inflammatory cytokines in the circulation,liver and spleen,it is not known whether it could directly target the local production of pro-inflammatory cytokines within the sensory circumventricular organs (cvos) situated within the brain,but outside the blood-brain barrier. using inactivation of il-10,we,therefore,investigated whether il-10 could modulate the synthesis of pro-inflammatory cytokines within the sensory cvos,in particular the organum vasculosum laminae terminalis (ovlt) and area postrema (ap).findings: primary ovlt and ap microcultures were established from topographically excised rat pup brain tissue. the microcultures were pretreated with either il-10 antibodies (ab) (10 μl/350 μl medium) or phosphate-buffered saline (pbs) (10 μl/350 μl medium) before being incubated with lipopolysaccharide (lps) (100 μg/ml) or pbs in complete medium for 6 h. supernatants were removed from the microcultures after 6 h of incubation with lps and used for the determination of il-6 and tumor necrosis factor (tnf)-α. pre-treating the ovlt and ap microcultures with il-10 antibodies significantly enhanced the lps-induced increase in tnf-α and il-6 in the supernatant obtained from the microcultures.conclusions: our results show for the first time that the lps-induced release of pro-inflammatory cytokines in cells cultured from the ap and ovlt can be modulated in the presence of il-10 antibodies. thus,we have identified that the sensory cvos may have a key role to play in both the initiation and modulation of neuroinflammation. © 2013 harden et al.; licensee biomed central ltd.