Relevance of the guinea-pig necrotic inflammation footpad reaction to safety concerns with MDP-based adjuvants.
The guinea-pig necrotic inflammatory reaction described by Nagao and Tanaka was investigated to determine its possible relevance to tuberculin-positive individuals who may receive MDP-based adjuvants. The reaction was induced by a preparatory footpad injection of Mycobacterium tuberculosis in Freund's incomplete adjuvant (FIA) followed three weeks later by a provocative gluteal injection of muramyl dipeptide (MDP). Increased footpad swelling and necrosis occurred within 24 h. The reaction was also caused to a significantly lesser degree by a gluteal injection of the threonyl-MDP component of Syntex adjuvant SAF-m. Elicitation of the reaction in responsive animals was absolutely dependent on the presence of both FIA and M. tuberculosis at the reaction site. Animals injected in the right footpad with FIA plus M. tuberculosis and in the left footpad with M. tuberculosis alone responded to the provocative injection with necrosis in the right footpad only. The reaction therefore appears to have little potential relevance to the vaccination of tuberculin-positive humans.
Hjorth
R N
RN
Wyeth-Ayerst Research, Philadelphia, PA 19101.
Bonde
G M
GM
Piner
E D
ED
Goldberg
K M
KM
Levner
M H
MH
Hung
P P
PP
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D005260:Female; D005528:Foot / Q000473:pathology; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D012449:Safety
D000276:Adjuvants, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C054064:N-acetylmuramyl-threonyl-isoglutamine