Curative effects of recombinant human interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis

We have studied the effects of treatment with recombinant human (rh)IL-6 on clinical, histological and immunological parameters of protracted relapsin g (PR) experimental allergic encephalomyelitis (EAE) in DA rats. rhIL-6 (50 mug/rat subcutaneously/day) was given under three different regimens, as e arly prophylaxis, from 1 day prior to 14 days after immunization, in late p rophylaxis, from day +7 until day 21 post-immunization (p.i.) and therapeut ically to rats with clinical signs of EAE from day 14 to day 28 p.i. Althou gh rhIL-6 failed to modulate the course of PR-EAE when administered as the early prophylactic regimen, it exerted clear-cut favourable effects on the course of the disease if was administered either as later prophylactic or a s therapeutic treatment. Under these conditions, rhIL-6 accelerated recover y from EAE attacks and reduced/milded subsequent EAE episodes as compared t o either PBS- or heat-inactivated rhIL-6-treated control rats. In agreement with this clinical effect, relative to PBS-treated rats, the animals injec ted with rhIL-6 exhibited lower numbers of MHC class II+ and CD4(+) cells i n their spinal cords. rhIL-6-treatment also profoundly modulated the endoge nous cytokine network, the treated rats displaying increased numbers of spl een cells expressing mRNA transcripts of the anti-inflammatory cytokines IL -10 and TGF-beta along with simultaneously reduced numbers of mRNAs for TNF -alpha. In addition, upon ex vivo exposure to either myelin basic protein p eptide 63-88 (MBP63-88) or to phytoaemagglutinin A, the numbers of IFN-gamm a secreting splenocytes was also significantly reduced (ELISPOT analysis) i n rhIL-6-treated rats as compared to PBS-treated controls. (C) 2001 Elsevie r Science B.V. All rights reserved.