title: Miltefosine effectively modulates the cytokine milieu in Indian post kala-azar dermal leishmaniasis.
abstract: BACKGROUND
  The increasing incidence of unresponsiveness to antimonials in leishmaniasis prompted the use of newer drugs such as miltefosine. Miltefosine influences macrophage effector functions, but its effect on patients with post kala-azar dermal leishmaniasis (PKDL) has not been evaluated.
  
  
  METHODS
  The immunomodulatory activity of miltefosine was evaluated in patients with PKDL by studying the expression of activation markers (CD14 and CD16) and costimulatory molecules (CD80 and CD86) on circulating monocytes, levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 6, interleukin 1β, and interleukin 8) and anti-inflammatory cytokines (interleukin 10, transforming growth factor β, interleukin 4, and interleukin 13) in serum and peripheral blood mononuclear cell culture supernatants, and serum nitrite and arginase activity.
  
  
  RESULTS
  Miltefosine on circulating monocytes upregulated expression of CD16 and CD86 and reduced that of CD14. Miltefosine also induced a significant increase in circulating levels of pro-inflammatory cytokines with a concomitant decrease in anti-inflammatory cytokines. Its macrophage activating potential was evidenced by its ability to decrease serum arginase activity and increase serum nitrite.
  
  
  CONCLUSIONS
  Miltefosine increased the proportion of monocytes that have a pro-inflammatory phenotype, which was accompanied by an enhanced secretion of pro-inflammatory cytokines and increased levels of serum nitrite. The decrease in anti-inflammatory cytokine levels and serum arginase activity collectively indicated that miltefosine triggered a robust T-helper 1 response that facilitated parasite elimination.
authors.affiliation: Department of Pharmacology, Institute of Post Graduate Medical Education and Research, India.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Mukhopadhyay
authors.forename: Nilay Kanti
authors.initials: NK
authors.lastname: Das
authors.forename: Susmita
authors.initials: S
authors.lastname: Roy
authors.forename: Sunanda
authors.initials: S
authors.lastname: Kundu
authors.forename: J N
authors.initials: JN
authors.lastname: Barbhuiya
authors.forename: Mitali
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007194:India; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017452:Receptors, IgG / Q000032:analysis; D044967:Serum / Q000737:chemistry; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007155:Immunologic Factors; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D010767:Phosphorylcholine; C039128:miltefosine