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Cytokines are important mediators of stroke-induced immunological/inflammatory reaction which contributes to brain infarct progression as well as to the disease severity and outcome. The aim of the study was to evaluate the levels of the proinflammatory and immunomodulatory cytokine interleukin-12 (IL-12) in serum of acute ischemic stroke patients, and to investigate the relation between these levels and demographic, laboratory, neuroimaging, and clinical data. The study comprised 23 first-ever ischemic stroke patients and 15 age- and sex-matched controls. Blood sampling for the determination of IL-12 and such peripheral markers of inflammation as erythrocyte sedimentation rate (ESR) and leukocyte count, together with cranial CT were performed within 24 h of stroke, while neurological and functional deficits were estimated, respectively, with the Scandinavian Stroke Scale (SSS) and Barthel Index (BI) within the same period and two weeks later. Stroke patients displayed significantly higher serum IL-12 levels in comparison with controls. The serum IL-12 levels in stroke patients correlated significantly with the ESR values, the volume of early brain CT hypodense areas, and with the SSS and BI scores calculated within both studied times. The results indirectly suggest that IL-12 may play a role in the pathophysiology of ischemic stroke.

Inflammation, involving cytokine/chemokine expression, occurs after stroke and deteriorates its course with leukocyte-mediated brain infarct progression. Chemokines are cytokines attracting selective leukocyte subsets and subgrouping into the four major subfamilies, CC, CXC, C, and CX3C. The CC subfamily preferentially acts on mononuclears. The study aimed to define serum CCL2, CCL3 and CCL5 levels in stroke patients and their relationship to the extent of disease severity and outcome. 27 ischaemic stroke patients and 20 controls were studied. Blood sampling for the determination of chemokines was performed at days 1, 2 and 3 of stroke, while neurological and functional deficits were estimated, respectively, with the Scandinavian Stroke Scale (SSS) and Barthel Index (BI) at the same time points and at days 14 and 28. Serum CCL3 levels at days 1, 2 and 3 of stroke were significantly higher than in controls. Serum CCL2 and CCL5 levels in stroke patients did not differ from those in controls at any of the time points examined. Serum chemokine levels in stroke studied separately did not differ between each other at any time point studied and demonstrated considerable variability. No correlation between serum chemokine levels and SSS scores was observed. Serum CCL2 and CCL3 levels at days 1, 2 and 3 of stroke correlated with BI scores at day 28. Serum CCL2 levels at days 2 and 3 of stroke also correlated with BI scores at day 14. Serum CCL5 levels at day 2 of stroke correlated with BI scores at day 28. The early and sustained increase in serum CCL3 levels in stroke patients along with correlation between them and short-term poststroke functional disability could indicate that the chemokine response may predispose to poor stroke outcome. The relationship between non-increased serum CCL2 and CCL5 levels and worse stroke outcome seems to be coincidental. Overall, as a result of large interindividual variability, CCL2, CCL3 and CCL5 are not reliable candidates for surrogate markers in stroke.

The inflammation accompanies and exacerbates cerebral ischaemia. The infiltrated leucocytes are thought to contribute to tissue injury in stroke patients. GRO-alpha (CXCL1) is a potent neutrophil chemoattractant which may play an important role in pathophysiology of stroke. 23 ischaemic stroke patients and 15 controls have been studied. CSF and blood sampling together with cranial CT were performed within first 24 hours of stroke. CXCL1 levels were determined by ELISA, and volume of stroke-related brain CT hypodense areas was calculated. Stroke patients displayed significantly higher CSF CXCL1 level than controls (65.6+/-22.3 vs 43.8+/-2.3 pg/ml; p<0.01). Serum CXCL1 levels in stroke patients did not differ from controls. CSF CXCL1 level correlated positively with volume of brain CT hypodense areas (p<0.001). The results suggest that CXCL1 may be involved in inflammatory reaction during an early phase of ischaemic stroke.

The MCP-1 and RANTES levels were measured in 20 multiple sclerosis patients before and after 1 year daily treatment with 20 mg of subcutaneously applied glatiramer acetate. The level of MCP-1 in serum from multiple sclerosis patients was lower than in control subjects. After one year of therapy with glatiramer acetate, the level of MCP-1 was almost identical with that at the starting point. The concentration of RANTES in MS, both before and after therapy, did not differ from the control subjects. The results emphasise the marked difference between the influence of glatiramer acetate and IFNbeta-1a on the expression of the studied cytokine. Glatiramer acetate therapy in multiple sclerosis is not so much an effective as a protective factor of antiinflammatory cytokines, it should be regarded as a down-regulator of proinflammatory agents.

Chemokines play an important role in pathogenesis of multiple sclerosis (MS), mediating migration of leukocytes into the central nervous system. CCL2 (MCP-1) chemokine is expressed in astrocytes in MS lesions. The aim of the study was to evaluate the effect of a two-year treatment with IFN-beta 1a on serum CCL2 level in MS patients. CCL2 concentration in sera of 18 relapsing-remitting MS (RR-MS) patients, and of 16 healthy controls was measured by ELISA. MS patients were treated with interferon-beta 1a (Avonex) in a dose of 30 microg i.m. once weekly. Significantly lower serum CCL2 level was found in MS patients in comparison with results of the control group. CCL2 concentration increased significantly after one year of therapy with IFN-beta, and remained high after the two-year treatment. The therapy of relapsing-remitting MS patients with interferon beta 1a is associated with a significant increase in CCL2 serum concentration.

Interleukin-15 is a novel cytokine produced by monocytes/macrophages and sharing several biological activities with IL-2. IL-15 induces T cell proliferation, enhances natural killer (NK) cell cytotoxicity and also stimulates B cells to proliferate and secrete immunoglobulins. The purpose of our study was to measure IL-15 levels in the serum and CSF of 21 patients with relapsing-remitting form of MS, 9 with active gadolinium enhancing lesions in MRI, 12 without enhancing MRI lesions and to compare the results with the control group. IL-15 levels were measured by ELISA. We found a significant increase of IL-15 in the sera of patients with MS in comparison with the control group consisting of 8 patients with tension headache. IL-15 serum levels were highest in patients with active, gadolinium enhancing lesions. IL-15 CSF levels were low and there was no difference between studied groups. The results may suggest the contribution of IL-15 in the immunopathogenesis of multiple sclerosis.

Proinflammatory cytokines produced by Th-1 cells and cytokines with immunosuppressive properties play an important role in the pathogenesis of multiple sclerosis (MS). Glatiramer acetate (GA) is one of the most important immunomodulatory agents used in the therapy of MS. The mechanism of action of GA in MS is not yet fully explained. In our previous study we found the significant down-regulation of interleukin 18 (IL-18), a proinflammatory cytokine inducing the production of interferon gamma during therapy with GA in MS patients. The purpose of this study was to evaluate the effect of GA in a dose 20 mg daily in a period of 6 months on interleukins IL-10 and IL-12. Thirty-one patients with definite MS and 30 control subjects were the subject of our study. The interleukins levels in sera were measured by the ELISA test. A significant increase was found of IL-12 and also of IL-10 levels in MS patients in comparison with control group. We also established a significant decrease of IL-12 after 3 and 6 months of GA therapy and some insignificant differences in the level of IL-10 (the decrease after 3 months and the increase after 6 months). IL-12 is a proinflammatory cytokine secreted by blood mononuclear cells, including dendritic cells in response to antigens and mitogens and is thought to contribute to the pathogenesis of MS. Therefore the established downregulation of IL-12 as well as that previously described of IL-18 suggest a marked relationship between the clinical effect and downregulatory action of GA on proinflammatory interleukins. The insignificant change of IL-10 level observed in the course of GA therapy seems to indicate that this cytokine is not connected with the immunomodulatory effect of GA in MS.