Increased expression of beta-chemokines in muscle of patients with inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are muscle diseases of autoimmune pathogenesis characterized by mononuclear cell infiltration within muscle tissue. Since immune cell homing and accumulation at the site of antigenic challenge is usually mediated by chemokines, we evaluated the expression of 2 beta-chemokines--monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)--by immunohistochemistry and polymerase chain reaction in muscles of polymyositis, inclusion body myositis, and dermatomyositis patients, and related their expression to immunopathological alterations in muscle. MCP-1 and MIP-1alpha transcripts were detected by PCR in all IIM muscles, but not in controls. By immunohistochemistry, the chemokines were found in all IIM muscle sections located in infiltrating inflammatory cells and also in neighboring extracellular matrix. The extent to which extracellular matrix was filled by each chemokine differed in each disease. In view of the known ability of chemokines to bind extracellular matrix and their possible synthesis by extracellular matrix components, we suggest that chemokine storage in the extracellular matrix can act as a microenvironmental factor amplifying lymphocyte activation and migration, thereby maintaining the autoimmune attack against unknown muscle antigens.

Prefrontal lactate predicts exercise-induced cognitive dysfunction in Gulf War Illness.

BACKGROUND: 25% to 30% of Veterans deployed to the 1990 to 1991 Persian Gulf War exhibit an idiopathic syndrome of chronic fatigue, exertional exhaustion, pain, hyperalgesia, cognitive and affective dysfunction known as Gulf War Illness (GWI). METHODS: Gulf War veterans (n=15) and sedentary veteran and civilian controls (n=11) completed a 2-back working memory test in an fMRI before and after two bicycle exercise stress test. We performed single voxel (1)H MRS to evaluate brain metabolic differences in the left anterior cingulate cortex and the changes associated with exercise. RESULTS: Eight GWI subjects increased their 2-back scores after exercise (labelled increasers) and seven GWI subjects decreased their 2-back scores after exercise (labelled decreasers). These phenotypic responses were absent for controls. Decreasers had significantly elevated prefrontal lactate levels compared to Increasers prior to completion of the exercise stress tests. Evaluation of prefrontal lactate levels prior to exercise demonstrated predictability (ROC analysis) of the two diametrically opposed subgroups. CONCLUSION: Prefrontal lactate levels may be a potential biomarker for exercise-induced subgroups in GWI. The alterations in brain energetics may be in part responsible for a subgroup of GWI and underlie some of the symptoms present in the patient population.

Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.

Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.