Submitted December 30, 2008
Accepted February 15, 2009
Cytokine changes during rituximab therapy in HIV-associated multicentric Castleman disease
Mark Bower, Ophelia Veraitch, Richard Szydlo, Peter Charles, Peter Kelleher, Brian Gazzard, Mark Nelson, and Justin Stebbing*
Department of Oncology, HIV Medicine and Immunology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom
Department of Oncology, Imperial College School of Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom
Department of Statistics, Imperial College School of Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom
Department of Biochemistry, Imperial College School of Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom
* Corresponding author; email: j.stebbing{at}imperial.ac.uk.
Recent data highlight the importance of inflammatory markers during human immunodeficiency virus type-1 (HIV) infection. HIV-associated multicentric Castleman Disease (HIV-MCD) presents with systemic symptoms attributed to cytokine disarray and we have previously shown that the use of the anti-CD20 monoclonal antibody rituximab induces clinical remissions. Before and during successful rituximab therapy, 15 plasma cytokines were measured as were adaptive (CD4, CD8, CD19) and innate (CD16/56) immune cell populations and HIV-1 viral loads. A significant reduction from baseline of the CD19 B cell count, consistent with rituximab's mechanism of action was observed. Markedly elevated cytokine levels were observed prior to rituximab therapy and a reduction from baseline values with rituximab therapy was observed for interleukin (IL)-5, IL-6 and IL-10. Therapies that reduce the inflammatory cytokine response are likely to be successful in a range of diseases, including HIV-MCD, and in the future may be used to guide therapeutic strategies.
