The proinflammatory cytokine interferon gamma (IFG) is elevated in body fluids of multiple sclerosis patients but its variation range is broad. The reason for this wide scatter of IFG production is not yet known. We looked for the relation between clinical parameters such as disability, exacerbation frequency, disease duration, course of the disease and IFG producing blood lymphocytes. Forty-one consecutive, clinically stable multiple sclerosis patients with primary relapsing course of the disease and without immunomodulatory or immunosuppressive treatment in the last 3 months were investigated for IFG in blood lymphocytes by flow cytometry. A significant positive correlation between IFG production and disability (r = 0.45, P50.01, Spearman's rho coefficient) was found. Pathophysiological implications and therapeutical relevance of this unexpected finding are discussed.
Olsson T. (1994) Multiple sclerosis: cerebrospinal fluid . Ann Neurol36 (Suppl) 100-102 .
2.
Cannella B , Raine CS. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions . Ann Neurol37: 424-435 .
3.
Navikas V , Link H. (1997) Review: cytokines and the pathogenesis of multiple sclerosis . J Neurosci Res45: 322-333 .
4.
Panitch HS , Hirsch RL , Haley AS , Johnson KP. (1987) Exacerbation of multiple sclerosis in patients treated with gamma interferon . Lancet1: 893-895 .
5.
Noronha A , Toscas A , Jensen MA. (1993) Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis . J Neuroimmunol46: 145-154 .
6.
Dayal AS , Jensen MA , Lledo A , Arnason BGW. (1995) Interferon-gamma-secreting cells in multiple sclerosis patients treated with interferon beta-1b . Neurology45: 2173-2177 .
7.
Phillippe Jet al. (1996) In vitro TNF-alpha, IL-2 and IFN-gamma production as markers of relapses in multiple sclerosis . Clin Neurol Neurosurg98: 286-290 .
8.
Dettke M , Scheidt P , Prange H , Kirchner H. (1997) Correlation between interferon production and clinical disease activity in patients with multiple sclerosis . JClin Immunol17: 293-300 .
9.
Crucian Bet al. (1995) Alterations in peripheral blood mononuclear cell cytokine production in response to phytohemagglutinin in multiple sclerosis patients . Clin Diagn Lab Immunol2: 766-769 .
10.
Revel Met al. (1995) Antagonism of interferon beta on interferon gamma: inhibition of signal transduction in vitro and reduction of serum levels in multiple sclerosis patients . Multiple Sclerosis1 (Suppl 1): 5-11 .
11.
Petereit HF , Bamborschke S , Esse AD , Heiss WD. (1997) Interferon gamma producing blood lymphocytes are decreased by interferon beta therapy in patients with multiple sclerosis . Multiple Sclerosis3: 180-183 .
12.
Link H. (1998) The cytokine storm in multiple sclerosis . Multiple Sclerosis4: 12-15 .
13.
Sharif MK , Hentges R. (1991) Association between tumor necrosis factor alpha and disease progression in patients with multiple sclerosis . New Engl J Med325: 467-542 .
14.
McDonnell GV , Hawkins SA. (1996) Primary progressive multiple sclerosis: a distinct syndrome ? Multiple Sclerosis2: 137-141 .
15.
Kurtzke JFet al. (1977) Studies on the natural history of multiple sclerosis . J Chron Dis30: 819-830 .
16.
Thompson AJet al. (1986) A clinical and laboratory study of benign multiple sclerosis . Quart J Med58: 69-80 .
17.
Kurtzke JF. (1983) Rating neurological impairment in multiple sclerosis: an expanded disability rating scale (EDSS) . Neurology13: 1444-1452 .
Jackson HJ , McGorry PD , Dudgeon P (1995) Prodromal symptoms of schizophrenia in first-episode patients: prevalence and specificity . Comprehensive Psych36: 241-250 .
20.
The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group . (1995) Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial . Neurology45: 1277-1285 .
21.
Gawne-Cain MLet al. (1998) MRI lesion volume measurement in multiple sclerosis and its correlation with disability: a comparison of fast fluid attenuated inversion recovery and spin echo sequences . JNeurol Neurosurg Psych64: 197-203 .
22.
O'Riordan JIet al. (1998) The prognostic value of brain MRI in clinically isolated syndroms of the CNS. A 10- year follow-up . Brain121: 495-503 .
23.
Evans AC , Frank JA , Antel J , Miller DH. (1997) The role of MRI in clinical trials of Multiple sclerosis: comparison of image processing techniques . Ann Neurol41: 125-132 .
24.
Campell IL , Iscaro A , Harrison LC. (1988) IFN-gamma and tumor necrosis factor alpha. Cytotoxicity to murine islets of Langerhans . J Immunol141: 2325-2329 .
25.
Adamson GM , Billings RE. (1993) Cytokine toxicity and induction of NO synthase activity in cultured mouse hepatocytes . Toxicol Appl Pharmacol119: 100-107 .
26.
Arnason BGet al. (1997) Role of interferons in demyelinating diseases . J Neural Transmission (Suppl 49): 117-123 .
27.
Vartanian T , Li Y , Zhao M , Stefansson K. (1995) Interferon gamma induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis . Molecular Med1: 732-743 .
28.
Moreau Tet al. (1996) Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis . Brain119: 225-237 .
29.
Trapp BDet al. (1998) Axonal transection in the lesions of multiple sclerosis . N Engl J Med338: 278-285 .
30.
Fergueson B , Matyszak MK , Esiri MM , Perry VH. (1997) Axonal damage in acute multiple sclerosis lesions . Brain120: 393-399 .
31.
Chao CCet al. (1992) Activated microglia mediate neuronal cell injury via a nitric oxide mechanism . J Immunol149: 2736-2741 .
