Discontinuation of treatment with IFN- β leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN- β and excessive expansion of autoreactive T cells as disease promoting mechanisms

• Published in: Journal of neuroimmunology 1998-04, Vol.84 (1), p.14-23
• Main Authors: van der Meide, Peter H, de Labie, Miranda C.D.C, Ruuls, Sigrid R, Groenestein, Reno J, Botman, Carolien A.D, Olsson, Tomas, Dijkstra, Christine D
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Disease Models, Animal; ELISPOT; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Experimental autoimmune encephalomyelitis; Female; IFN- β; Interferon-beta - administration & dosage; Lewis rats; Lymph Nodes - drug effects; Lymph Nodes - physiology; Medicin och hälsovetenskap; Multiple Sclerosis - metabolism; Rats; Rats, Inbred Lew; Recurrence; Spleen - drug effects; Spleen - physiology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(97)00207-5

IFN- β has recently been shown to exert remarkable beneficial effects on disease development in patients with early stage relapsing-remitting MS. The specific immune mechanism(s) by which IFN- β ameliorates this human demyelinating disease is at present undefined. One potential mechanism may reside in the antiproliferative activity of IFN- β which may inhibit the expansion of autoaggressive T cells thereby limiting disease progression. In the present study we investigated whether the administration of recombinant rat IFN- β (rrIFN- β) to Lewis rats with actively induced experimental autoimmune encephalomyelitis (EAE) inhibits the expansion of encephalitogenic T cells in lymphoid organs and as such may contribute to suppression of disease activity in this widely used animal model for MS. Our data show that daily administrations of ≥3×10 5 u rrIFN- β to EAE rats, starting two days before MBP sensitization and continued for 10 days led to a dramatic and dose-dependent reduction in encephalitogenic T cells in both spleen and inguinal lymph nodes at day 8 post-immunization (p.i.). However, the rrIFN- β-mediated reduction in effector T cells did not ameliorate paralytic disease as expected but significantly enhanced the severity of EAE. Analyses of lymphoid organs in the remission phase of EAE revealed strongly elevated numbers of encephalitogenic T cells in rrIFN- β-treated versus control rats suggesting a rapid reversal of the antiproliferative action of rrIFN- β followed by an overshoot in the subsequent expansion of these effector T cells. In conformity with higher numbers of encephalitogenic T cells and worsening of disease, animals also showed significantly greater perivascular inflammation in the CNS. The relevance of our findings in relation to the beneficial effects of IFN- β in MS is discussed.