Splenic cytokine responses in Indian kala-azar before and after treatment.
Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma; n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute.
Kenney
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RT
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. kenney@cber.fda.gov
Sacks
D L
DL
Gam
A A
AA
Murray
H W
HW
Sundar
S
S
D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000494:pharmacology; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004338:Drug Combinations; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010715:Phosphatidylglycerols / Q000494:pharmacology; D013154:Spleen / Q000276:immunology*
D016207:Cytokines; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D016753:Interleukin-10; D015847:Interleukin-4; D000666:Amphotericin B; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate