Little is known about the involvement of cytokines in the pathogenesis of primary progressive (PP) multiple sclerosis (MS). We evaluated in this cross-sectional study whether IL-18, IL-12p35, IL-12p40, TNF-α, IFN-γ, IL-10, IL-4, TGF-β, IL-12Rβ1, and IL-12Rβ2 mRNA expression in unstimulated white blood cells showed significant differences between relapsing-remitting (RR), secondary progressive (SP) and PP MS patients, and healthy controls. All clinical subtypes showed unique mRNA expression patterns as compared to the controls. Both RR and SP patients displayed increased levels of IL-12p40, IL-18, and TGF-β mRNA compared to controls, whereas PP patients showed only increased IL-18 mRNA levels. Both in PP and SP patients, IFN-γ and IL-10 mRNA were decreased compared to RR patients and controls. PP patients were unique in that they showed decreased IL-12Rβ1 mRNA. In conclusion, our data show that the assessment of cytokine (receptor) mRNA profiles is useful to discriminate between the different clinical subtypes and suggest that different cytokines are involved in the pathogenesis of PP MS as compared to RR and SP MS. © 2001 Elsevier Science B.V. All rights reserved. Chemicals/CAS: Cytokines; Interleukin-10, 130068-27-8; Interleukin-12, 187348-17-0; Interleukin-18; Receptors, Interleukin; Receptors, Interleukin-12; RNA, Messenger; Transforming Growth Factor beta