Significant HIV effects were found on seven of the thirteen cytokines, primarily with respect to interleukins. neurocognitive performance. Significant HIV effects were found on seven of the thirteen cytokines, primarily with respect to interleukins. HIV clinical factors (CD4 and HIV RNA levels, duration of illness, antiretroviral treatment) and hepatitis C status were associated with specific plasma cytokine concentrations. Neurocognitive measures were associated with cytokine concentrations, most consistently among the interleukins and IP-10. Generally, cytokine concentrations were among the strongest predictors of neurocognitive function relative to other clinical factors, which reinforces Goat monoclonal antibody to Goat antiRabbit IgG HRP. their potential importance in examining the neuropathological processes of HIV. The findings also point to the potential value of simultaneously examining a panel of biomarkers. The current results suggest that a complex relationship likely exists among cytokines [how?], and that these relationships are mediated not only by HIV contamination, but also by antiretroviral treatment and other comorbid conditions. == INTRODUCTION == HIV-associated neurocognitive and behavioral disturbances are well recognized, and continue to occur despite widespread use of highly active antiretroviral therapies (HAART), which can 1-Methylguanosine very effectively reduce HIV RNA level and enhances the host immune status. HIV crosses the blood brain barrier and enters the brain very soon after initial contamination and replicates in perivascular macrophages and microglia1. In this regard, HIV contamination triggers inflammatory responses associated with microglial cell activation and attendant release of neurotoxic pro-inflammatory cytokines2-4. 1-Methylguanosine The inflammatory component of HIV contamination in the central nervous system (CNS) is regarded as a critical component of HIV-associated brain dysfunction5-10, with its severity strongly correlating with the abundance of activated monocytes in the brain11. HIV-associated neuronal loss and dysfunction are mediated by increased apoptosis and axonal degeneration throughout the brain12-14. Frontal-striatal areas have been implicated15-21, consistent with findings of attention-executive and psychomotor impairments common in HIV-infected persons. Neuroimaging approaches, such as magnetic resonance spectroscopy (MRS), can detect abnormalities that reflect cerebral inflammation in HIV infected people22-24. Previous MRS studies in HIV have shown abnormal cerebral metabolites preferentially in the basal ganglia and frontal brain regions. Moreover, specific metabolite levels were demonstrated to be altered in relation to cognitive impairment and brain atrophy23-26. Cytokines, especially those with chemotactic properties (chemokines) are thought to play important roles in HIV-related neuronal injury and protection5-8,19,27-37. Increased levels of chemokine gene expression are detectable in brains with HIV encephalitis, and altered levels of various chemokines and cytokines can be measured in the CSF of patients with HIV-associated dementia11,29,38-44. Serum or plasma cytokine levels have been found to be either increased or decreased in HIV-infected individuals, depending on the specific cytokine and on disease status, such as bodily wasting associated with AIDS45-47. In one study, elevated levels of various plasma cytokines were correlated with cognitive impairment in HIV47. Correspondingly, elevated plasma cytokine concentrations have been linked to cognitive impairment 1-Methylguanosine in other diseases, including multiple sclerosis and Alzheimers 1-Methylguanosine Disease/moderate cognitive impairment48-60, in which inflammation is thought to exacerbate the underlying disease process. While the bases for cytokines effects on cognition are not well comprehended, plasma cytokines could be used as peripheral indices of CNS pathology, in concert with neuroimaging and neurocognitive testing, and therefore are of interest as 1-Methylguanosine potential biomarkers for assessing HIV-associated brain dysfunction. Accordingly, we were interested in better understanding the relationship between plasma cytokine levels and cognitive function in HIV. In the present study, we measured plasma cytokines and chemokines in 30 HIV-infected and 34 seronegative individuals enrolled in a prospective study of HIV-associated brain dysfunction. Statistical analyses were performed to identify the plasma markers that were most strongly associated with neurocognitive function, after accounting for HIV clinical factors (e.g., nadir CD4, duration of contamination). Given the preponderance of past findings of cognitive deficits in attention/executive functioning and processing velocity in HIV-infected individuals61,62, we hypothesized that performance in these cognitive domains would be associated with broad-ranging abnormalities of plasma cytokine activation. == METHODS == == Clinical Sample == All subjects were enrolled in a Brown University Center for AIDS Research study to examine the effects of HIV on brain function. Informed consent was obtained from all participants. All subjects underwent a clinical evaluation which included a detailed medical history and assessment of HIV disease. Potential participants were excluded if they had evidence of other neurological brain disease (e.g. Alzheimers disease), traumatic brain injury with loss of consciousness of greater than 10 minutes, prior opportunistic brain infection secondary to HIV,.