In this paper the author will review a few of the more recently developed natural and synthetic agents that have been used to deplete C levels in animals. In some instances, these studies have revealed the significant role of specific C components in various immediate or delayed forms of hypersensitivity. In other cases, the C system was important in host defense mechanisms, possibly for tumor-regressing activity, and in inflammatory reactions under circumstances where activation by the classical immune pathway involving antigen-antibody interactions was not always involved. Additional information has been gained in evaluating the usefulness of some of the agents for treatment of disorders, some of which are associated with inflammatory processes caused by the activation of the C system in animals and in human subjects. Studies of various C inhibitory agents for the purpose of inducing deficiencies in animals have uncovered at least five fundamental problems: some agents that inhibit the action of C in vitro may not have the same primary target in vivo; because of their intrinsic chemical properties, the agents may be too toxic for use in animals; the halflife of the active form of the agent in vivo may be too short; an agent may be antigenic, and eventually specific antibodies neutralize its anticomplementary action; an agent may have too large a volume of distribution in vivo and be rapidly cleared from the circulation. These problems must be considered when testing an agent for anti-C activity in vivo. Unless an individual C component is activated directly, the C system is a cascade of protein-protein interactions. An agent that inactivates the C proteins early in the sequence of reactions in either the classic or alternative C pathway may be of benefit in preventing tissue injury from C-dependent cytolytic and cytotoxic reactions. In fact, this approach was recognized by Osborn in 1937: 'if complement action is, as it seems, a chain reaction depending on the successive action of several factors, it may be expected that the least active constituent will limit the activity of the complex as a whole'.
|Original language||English (US)|
|Number of pages||22|
|Journal||Progress in Allergy|
|State||Published - Jan 1 1986|
ASJC Scopus subject areas
- Immunology and Allergy