Prednisolone mediated suppression of HIV-1 viral load strongly correlates with C-C chemokine CCL2: In vivo and in vitro findings.
CCL2 (MCP-1) is a proinflammatory chemokine induced in HIV-1 infection. We have previously demonstrated a significant correlation of CCL2 gene expression with HIV-1 viremia. In this study we investigated the effect of prednisolone on CCL2 gene expression and viral load in an HIV-1-infected patient receiving high-dose prednisolone for severe uveitis. We observed a >1 log reduction of HIV-1 viral load, associated with more than hundred fold reduction of CCL2 expression at day 3 of prednisolone treatment. In vitro HIV-1 infection of PBMC demonstrated reduced HIV-1 replication in the presence of prednisolone. Flow cytometric analysis revealed 50% reduction of LTR driven GFP activity by prednisolone in GHOST cells. These findings indicate that prednisolone suppresses both HIV-1 viral load and CCL2 mRNA expression, an association which might be exploited for future anti-inflammatory therapeutic strategies in HIV-1 infection.
Ansari
Abdul Wahid
AW
Department of Clinical Immunology, Hannover Medical School, Carl-Neuberg-Str 1, D-30625, Hannover, Germany.
Schmidt
Reinhold E
RE
Heiken
Hans
H
D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects; D014605:Uveitis / Q000188:drug therapy / Q000209:etiology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy; D015215:Zidovudine / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D000893:Anti-Inflammatory Agents; D048588:Benzoxazines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003521:Cyclopropanes; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019259:Lamivudine; D015215:Zidovudine; D011239:Prednisolone; C098320:efavirenz