Intradermal anti-loxosceles Fab fragments attenuate dermonecrotic arachnidism.
OBJECTIVE
Bites from the brown recluse spider and other arachnids from the genus Loxosceles frequently induce necrotic skin lesions that can be recalcitrant to treatment and disfiguring. The authors used a rabbit model of dermonecrotic arachnidism to address the therapeutic efficacy of intradermal (id) polyclonal anti-Loxosceles Fab fragments (alphaLoxd Fab) raised against Loxosceles deserta spider venom.


METHODS
Fab fragments were prepared by papain digestion and affinity chromatography from the IgG fraction of L. deserta antivenom raised in rabbits. Eighteen inbred New Zealand white rabbits were assigned to six groups of three. The rabbits received L. deserta venom (3 microg, id) injections into each flank. Cohorts of rabbits received single id injections (at one venom site/rabbit) of 30 microg alphaLoxd Fab at different times (T = 0, 1, 2, 4, 8, and 12 hours) after venom injection. In each rabbit the opposite flank was left untreated. As an additional control, one group of rabbits (T = 0) received nonspecific Fab (30 microg, id) in the opposite flank. Dermal lesions were quantified as a function of time through the use of a series of digital photographs and imaging software. In addition, myeloperoxidase (MPO) activity, a measure ofneutrophil accumulation, was determined in lesion biopsies. Lesion areas and MPO activities were analyzed by repeated-measures analysis of variance (ANOVA).


RESULTS
Lesion areas and MPO activity were markedly reduced when alphaLoxd Fab was administered very early after venom injections. As the interval between venom inoculation and antivenom treatment increased, the therapeutic benefit of alphaLoxd Fab decreased. The final time tested that demonstrated therapeutic efficacy of alphaLoxd Fab was T = 4 hours. Lesion attenuation was no longer apparent when alphaLoxd Fab was given 8 hours post inoculation.


CONCLUSIONS
Intradermal administration of alphaLoxd Fab attenuates Loxosceles-induced dermonecrotic lesion formation when given up to 4 hours after venom inoculation in this rabbit model.
Gomez
H F
HF
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0305, USA. hfg@umich.edu
Miller
M J
MJ
Trachy
J W
JW
Marks
R M
RM
Warren
J S
JS
D000704:Analysis of Variance; D000818:Animals; D000997:Antivenins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D007271:Injections, Intradermal; D016209:Interleukin-8 / Q000032:analysis; D009336:Necrosis; D010865:Pilot Projects; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D001098:Spider Bites / Q000188:drug therapy* / Q000276:immunology; D013111:Spider Venoms / Q000276:immunology; D013112:Spiders; D016896:Treatment Outcome
D000997:Antivenins; D007140:Immunoglobulin Fab Fragments; D016209:Interleukin-8; D013111:Spider Venoms