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Immunological heterogeneity of multiple sclerosis in Sardinia and SwedenDivision of Neuroimmunology, Neurotec Department, Karolinska Institute, Stockholm, Sweden, yu-min.huang{at}neurotec.ki.se
Division of Neuroimmunology, Neurotec Department, Karolinska Institute, Stockholm, Sweden
Department of Biosciences, Karolinska Institute at NOVUM, Huddinge, Sweden
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Division of Neuroimmunology, Neurotec Department, Karolinska Institute, Stockholm, Sweden Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes. Although ethnically distant, both populations have similarly high multiple sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their receptors, signalling molecules and other immune response-associated factors might influence MS pathogenesis, though definite proof is missing. The study of populations with similar MS incidence but different genetic and environmental background could make possible the definition of factors that relate to such background differences. We selected untreated female MS patients from Sassari, Sardinia, and Stockholm, Sweden, and corresponding sexand age-matched healthy controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20 immune response-related genes considered relevant in MS, employing real-time PCR. Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and Stockholm, compared to corresponding HC. MS patients from Sassari, but not Stockholm, expressed higher TNF-a compared to corresponding HC. MS patients from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3 dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS from Stockholm compared to corresponding HC. This was not observed in Sassari. No differences were detected for other members of the IL-12 family, other Th1 and Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-a and IL-6, although the extent of expression of TNF-a, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas. This might result from genetic and/or environmental differences. They may account for some of the discrepancies regarding immune response-related molecules previously reported in MS. In conclusion, a pro-inflammatory state exists in MS patients from Sassari as well as Stockholm. The changes of pro-inflammatory and other immune response-related variables differ however between the two MS populations. This may be attributed to the genetic and/or environmental background.
Key Words: IDO IL-6 IL-12 multiple sclerosis RT-PCR TNF-
Multiple Sclerosis, Vol. 11, No. 1,
16-23 (2005) This article has been cited by other articles:
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