Pyrogen tolerance is another important reaction that develops when the animals are given repeated injections of a pyrogen. A reduced sensitivity to the same and other pyrogens develops which nullifies the febrile response and requires that the tolerant animal be withdrawn from further pyrogen testing. Although the rabbit is the most often used test animal, man is considered to be the most sensitive to pyrogens. There are two general kinds of bacterial toxins. Exotoxins are produced during the growth phase of certain kinds of bacteria and are liberated into the medium or tissue.
Exotoxins are protein in nature and their reactions are specific.
For example, Clostridium botulinum produces an exotoxin of unusual potency which affects only neurological tissue. Other well-known examples of exotoxins are tetanus toxin, Shiga toxin, and diphtheria toxin. Endotoxins are another kind of toxin that can be extracted from a wide variety of gram-negative bacteria. Higher doses of endotoxin are required to produce a lethal effect in the experimental animal than are required for exotoxins. The effects produced by endotoxins on the host are systemic such as fever and general body reactions, rather than strictly neurological effects, as is the case with most exotoxins.