In vivo effect of snake phospholipase A2 (crotoxin+cardiotoxin) on serum IL-1alpha, TNF-alpha and IL-1ra level in humans.
VRCTC-310-Onco (crotoxin, a secretory phospholipase A2+cardiotoxin) is under development as an anti-neoplastic agent. Pro-inflammatory cytokines TNF-alpha and interleukin 1 alpha (IL-1alpha) and anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) were measured with commercial ELISA kits in sera corresponding to 23 cycles with doses between 0.0025 and 0.023 microg/kg body weight, obtained during the phase I trial of VRCTC-310-Onco. Neither serum TNF-alpha nor IL-1alpha did change significantly after VRCTC-310-Onco. Basal IL-1ra was 794 +/- 97 pg/ml, by 3 h it was similar, 651 +/- 99 pg/ml and at 24 h p.i. it increased to 1197 +/- 122 pg/ml (P<0.001). The increase was dose-dependent. The addition of dexamethasone (required to reduce pain with the highest doses) inhibited IL-1alpha and enhanced the induction of IL-1ra by VRCTC-310-Onco. Summing up, in vivo, in humans, in the dose range tested, VRCTC-310-Onco induces IL-1ra, and does not consistently modify IL-1alpha or TNF-alpha serum levels.
Costa
L A
LA
Onco-Venom Research, School of Medicine (UBA), Av. del Libertador 4944, 7 degrees B 1426, Buenos Aires, Argentina. lcosta@ciudad.com.ar
Fornari
M C
MC
Berardi
V E
VE
Miles
H A
HA
Diez
R A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004179:Cobra Cardiotoxin Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D003439:Crotoxin / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D010741:Phospholipases A / Q000008:administration & dosage / Q000494:pharmacology*; D054467:Phospholipases A2; D012795:Sialoglycoproteins / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000970:Antineoplastic Agents; D004179:Cobra Cardiotoxin Proteins; C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003439:Crotoxin; D010741:Phospholipases A; D054467:Phospholipases A2