Qualitative immune modulation by interleukin-2 (IL-2) adjuvant therapy in immunological non responder HIV-infected patients.
BACKGROUND
Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs).


RESULTS
PBMC from 12 immunological non-responders (INRs) (CD4+<200/µl, HIV-RNA<50 cp/ml) on combination antiretroviral treatment (cART) were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs) and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01). Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02) and substantial reductions in IL-10 levels were observed.


CONCLUSIONS
IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone.
Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milan-Bicocca, Monza, Italy. f.sabbatini@hsgerardo.org
Francesca
F
Sabbatini
Alessandra
A
Bandera
Giulio
G
Ferrario
Daria
D
Trabattoni
Giulia
G
Marchetti
Fabio
F
Franzetti
Mario
M
Clerici
Andrea
A
Gori
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009162:Mycobacterium avium / Q000254:growth & development; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma