Effects of calcitriol on eosinophil activity and antibody responses in patients with schistosomiasis.
OBJECTIVE
Parasitic infestations are known to elicit T-helper lymphocyte type 2 (Th-2) reactions, characterized by a pronounced eosinophila and high IgE levels. In humans both elevated specific IgE levels and eosinophil counts are associated with resistance to reinfection with schistosomiasis. This study aimed to establish whether the Th-2 reaction could be enhanced with calcitriol (vitamin D3). Calcitriol has been shown to cause a shift from Th-1 to Th-2 type reactions when applied locally to the skin.


METHODS
Fifty-nine patients with Schistostoma haematobium infection were randomized to one of four treatment modalities, i.e. (a) praziquantel (PZQ) 60 mg.kg-1 orally on day 1, (b) PZQ 60 mg.kg-1 on day 1 plus calcitriol 1 microgram per day orally for 5 consecutive days, (c) calcitriol 1 microgram per day for 5 consecutive days or (d) placebo. Blood for differential counts, eosinophil cationic protein (ECP), specific IgE and IgG to whole-worm antigen, as well as urine samples for egg counts, were collected on days 0 and 21.


RESULTS
Baseline values did not differ significantly between the groups. Calcitriol alone resulted in significant increases in circulating lymphocytes (median increase of 5.5%) and the percentage of eosinophil vacuolization (mean increase 28%). It, however, significantly decreased ECP levels (mean decrease 46%). PZQ in combination with calcitriol significantly enhanced production of specific IgE (mean increase 213%) and IgG (mean increase of 170%) and tended to increase eosinophil vacuolization (mean increase 22%). All these changes also differed significantly from those in the placebo group. The specific IgE and IgG levels were also significantly higher than the already increased levels seen with PZQ treatment only. ECP levels were, however, not significantly affected by combination therapy, whereas PZQ alone significantly enhanced ECP production (mean increase 93%).


CONCLUSIONS
The increases in specific IgE responses and percentage of eosinophil vacuolization favour a Th-2 type of reaction. The ECP values viewed in isolation may, paradoxically, indicate a Th-1 response; this could, however, have been an artefact due to the method of ECP detection ex vivo. Finally, it would seem that calcitriol does cause some immune augmentation when combined with PZQ therapy in patients with schistosomiasis. However, long-term follow-up is needed to prove that these findings would translate into resistance against re-infection.
Snyman
J R
JR
Department of Pharmacology, Faculty of Medicine, University of Pretoria, South Africa.
de Sommers
K
K
Steinmann
M A
MA
Lizamore
D J
DJ
D000293:Adolescent; D001798:Blood Proteins / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D010270:Parasite Egg Count; D011223:Praziquantel / Q000627:therapeutic use; D012260:Ribonucleases; D012553:Schistosomiasis haematobia / Q000097:blood / Q000276:immunology* / Q000652:urine; D012556:Schistosomicides / Q000008:administration & dosage / Q000627:therapeutic use; D016037:Single-Blind Method
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007074:Immunoglobulin G; D012556:Schistosomicides; D007073:Immunoglobulin E; D011223:Praziquantel; D012260:Ribonucleases; D002117:Calcitriol