ABSTRACT
The in vitro effect of methylprednisolone on prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 (TXB2) synthesis by adherent monocytes was examined using samples of peripheral blood from 15 patients with multiple sclerosis and 18 normal controls. Eicosanoid production by monocytes was reduced in patients compared with controls and there was a dose-dependent inhibitory effect of methylprednisolone on eicosanoid production in both groups. In vitro production of PGE2 and TXB2 but not LTB4 was reduced in patients with multiple sclerosis following intravenous treatment with methylprednisolone compared with pretreatment samples. In a separate cohort of 20 patients with multiple sclerosis and 15 controls, the in vitro inhibition of PGE2 release by methylprednisolone was not associated with reduced pokeweed-mitogen-stimulated immunoglobulin G synthesis by peripheral blood mononuclear cells. These results suggest that methylprednisolone inhibits monocyte-macrophage function, but this effect is not specific to patients with multiple sclerosis.
Subject(s)
Dinoprostone/biosynthesis , Leukotriene B4/biosynthesis , Methylprednisolone/pharmacology , Monocytes/immunology , Multiple Sclerosis/immunology , Thromboxane B2/biosynthesis , Adult , Cells, Cultured , Dose-Response Relationship, Immunologic , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/analysis , Male , Monocytes/drug effects , Pokeweed Mitogens , RadioimmunoassayABSTRACT
Peripheral blood T cell phenotypes have been analysed in serial samples from patients with multiple sclerosis, their unaffected relatives and controls using a panel of antibodies chosen to distinguish T suppressor and activated suppressor cells from other CD8 lymphocytes. Overall, the percentage of Leu 2a cells correlated with alterations in the Leu 2a/15 suppressor sub-population (r = 0.79, p less than 0.001). Fewer circulating Leu 2a and Leu 2a/15 positive cells were identified in multiple sclerosis patients than unaffected individuals but there was no alteration in percentage of activated (Leu 2a/DR) CD8 cells. These findings suggest that the fluctuations in CD8 cells, characteristic of patients with multiple sclerosis, are due to alterations in T suppressor phenotype; this may then lower the threshold for activation of other T cell subpopulations.
Subject(s)
Multiple Sclerosis/immunology , T-Lymphocytes, Regulatory/immunology , CD4-Positive T-Lymphocytes/immunology , Female , Humans , Leukocyte Count , Male , Multiple Sclerosis/geneticsABSTRACT
A stronger association has been found between multiple sclerosis and HLA-DR2 than -DQwl in south east Wales (prevalence c 113/10(5)) in contrast to recent observations in north east Scotland (prevalence 178/10(5). The complex relationship between the HLA system and multiple sclerosis, demonstrated in this and other studies, is explained more easily under a polygenic model of inheritance, in which environmental events and genes interact, than by the presence of a single susceptibility gene.
Subject(s)
HLA Antigens/genetics , Multiple Sclerosis/genetics , Gene Frequency , Genetic Markers , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , HLA-DR2 Antigen , Humans , Risk Factors , WalesABSTRACT
Peripheral blood OKT8 cell phenotypes were correlated with measurements of plasma cortisol and serological evidence for exposure to 15 infectious agents, in longitudinal studies involving 13 patients with multiple sclerosis, 13 of their siblings, nine spouses and 13 unrelated controls; 44/48 individuals were HLA typed. Neither circadian rhythms, nor exposure to any one infectious agent accounted for the serial changes in OKT8 cells but there was an association between the presence of HLA-DR2 and periodic reductions in OKT8 cells irrespective of clinical status. Taken with previously reported serial observations in patients and cohabiting relatives, this finding provides indirect evidence for an interplay between environmental and genetic factors in determining OKT8 cell phenotypes in multiple sclerosis.
Subject(s)
Leukocyte Count , Multiple Sclerosis/immunology , T-Lymphocytes, Regulatory/immunology , Antibodies/analysis , Circadian Rhythm , HLA-DR Antigens/genetics , Humans , Multiple Sclerosis/genetics , Phenotype , Risk FactorsABSTRACT
Previous serial measurements of lymphocyte subpopulations in individuals with multiple sclerosis (MS) have demonstrated periodic reductions in the number of OKT8 positive (T8+) cells. In this longitudinal study, involving twice monthly samples from each participant and carried out in two phases lasting at least six and three months respectively, we have confirmed that fluctuations in T8+ cells occur in patients with MS and also found a significant reduction in this lymphocyte subpopulation in patients' spouses but not their siblings, compared with unrelated controls. The changes observed in spouses were related in time to those occurring in patients on 10/13 occasions from 5/9 families; no temporal relationship occurred in the remainder. Taking two or more low T8+ values as significant, 12/13 patients, 7/9 spouses, 6/13 siblings and 4/13 controls (chi 2 = 12.5; P less than 0.01) were abnormal at some stage. Our results provide indirect evidence for the role of environmental factors in determining certain immunological abnormalities present in patients with MS and illustrate the role of family studies in determining the specificity of these changes to the disease.
