RELEVANCE OF THE GUINEA-PIG NECROTIC INFLAMMATION FOOTPAD REACTION TOSAFETY CONCERNS WITH MDP-BASED ADJUVANTS

The guinea-pig necrotic inflammatory reaction described by Nagao and T anaka was investigated to determine its possible relevance to tubercul in-positive individuals who may receive MDP-based adjuvants. The react ion was induced by a preparatory footpad injection of Mycobacterium tu berculosis in Freund's incomplete adjuvant (FIA) followed three weeks later by a provocative gluteal injection of muramyl dipeptide (MDP). I ncreased footpad swelling and necrosis occurred within 24 h. The react ion was also caused to a significantly lesser degree by a gluteal inje ction of the threonyl-MDP component of Syntex adjuvant SAF-m. Elicitat ion of the reaction in responsive animals was absolutely dependent on the presence of both FIA and M. tuberculosis at the reaction site. Ani mals injected in the right footpad with FIA plus M. tuberculosis and i n the left footpad with M. tuberculosis alone responded to the provoca tive injection with necrosis in the right footpad only. The reaction t herefore appears to have little potential relevance to the vaccination of tuberculin-positive humans.