Multiparameter Analysis of Clastogenic Factors, Pro-oxidant Cytokines, and Inflammatory Markers in HIV-1-Infected Patients with Asymptomatic Disease, Opportunistic Infections, and Malignancies

Abstract

HIV-1-infected patients are in chronic oxidative stress and clastogenic factors (CFs) are present in their plasma. CFs from patients with HIV are formed via superoxide anion radical and stimulate further superoxide production. The pathophysiolgic significance and the exact composition of the circulating clastogenic material in patients with HIV is unknown. Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical study was to compare levels of CF in HIV-1-positive patients with asymptomatic disease, opportunistic infections, and malignancies with those in HIV-1-negative control groups and to correlate CF activity with CD4+ T cell numbers, the cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were significantly increased in all HIV-1-positive patients and in HIV-1-negative patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma showed the highest CF activity in their plasma (p < 0.08). CFs appear very early in HIV infection, and they correlate negatively with CD4+ T cells, which are an indicator of disease activity. The presence of CF in the plasma of HIV-infected patients is not a general response to a viral infection because these factors are not increased in HIV-1-negative patients with viral infection (zoster). CFs are not specific for the HIV-1 infection; they also occur in HIV-1-negative patients with malignant tumors. There was a tendency towards a positive correlation (p < 0.14) between CF and TNF-alpha but there was no positive correlation of CF with IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha may be among the components of CF in HIV-1-infected patients. In addition, other unidentified components may contribute to the clastogenic activity of the plasma or the composition of CF may vary from patient to patient. Further clinical studies with larger sample populations are necessary to analyze the composition of CF in HIV-1-positive patients.

Clastogenic Factors as Potential Biomarkers of Increased Superoxide Production

“…Vitamin C, selenium and zinc were at the lower limit of normal. On the opposite, vitamin A, E and beta carotene were in the normal range in all 22 patients of the study group, who were still in a satisfactory nutritional state (Fuchs et al 1998). …”

Developments in Neuroprotection for HIV-Associated Neurocognitive Disorders (HAND)

“…HIV infection induces pathological oxidative stress, as evidenced by diminished levels of reduced glutathione in plasma, lymphocytes, and PBMC and elevated levels of biomarkers of lipid peroxidation products such as malondialdehyde and hydroperoxide; several of these and other markers of oxidative stress correlate with disease progression and mortality [47][48][49][50][51]. Oxidative stress can in turn drive inflammation through enhancing NF-κB-driven HIV replication and release of proinflammatory cytokines [52][53][54][55].…”