Regulation of IL-5 in onchocerciasis. A critical role for IL-2.
The cytokine profiles of PBMC obtained from individuals "immune" to Onchocerca volvulus infection were compared to those from infected individuals. The immune individuals had significantly higher levels of both IL-2 and IL-5 in response to parasite Ag than did those individuals with active infection (mean IL-2 = 1.3 and 0.138 U/ml, respectively; mean IL-5 = 973 and 147.4 pg/ml, respectively), and there was a direct correlation between the production of IL-2 and IL-5. To examine the mechanism underlying the possible association between these two cytokines in patients infected with onchocerciasis, reverse transcription followed by polymerase chain reaction was used to measure IL-5 mRNA. In response to rIL-2, IL-5 mRNA appeared as early as early as 3 h after stimulation of patient PBMC, reaching a peak at 24 h; further, this response was inhibited with neutralizing antibodies to IL-2. IL-2 was unable to induce mRNA expression for IL-4, IFN-gamma, IL-10, or granulocyte-macrophage-CSF. To assess whether IL-2 was specifically responsible for the up-regulation of Ag-induced IL-5 production in patients with onchocerciasis, IL-5 mRNA expression was measured in PBMC stimulated with parasite Ag. Up-regulation of IL-5 mRNA was seen in all patients (peaking at 72 h) in response to Ag stimulation and was found to be independent of proliferation to Ag; in addition, this up-regulation was specifically inhibited by neutralizing anti-IL-2 antibodies. Further, the primary source of IL-5 mRNA was determined to be CD4+ T cells. These findings suggest that IL-2 production is required to induce IL-5 and further implicates IL-5 as a possible mediator of protection in onchocerciasis.
Steel
C
C
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Nutman
T B
TB
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D017181:Onchocerca volvulus / Q000276:immunology; D009855:Onchocerciasis / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D000947:Antigens, Helminth; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D011994:Recombinant Proteins