TOLERANCE TO BACTERIAL PYROGENS : I. FACTORS INFLUENCING ITS DEVELOPMENT

Area of Science:

• Immunology
• Microbiology
• Physiology

Background:

• Bacterial pyrogens, such as those from Eberthella typhosa, Serratia marcescens, and Pseudomonas aeruginosa, are known to induce fever.
• Understanding the development of tolerance to pyrogens is crucial for managing inflammatory responses and fever in various clinical settings.

Purpose of the Study:

• To investigate the pattern and characteristics of febrile responses and tolerance development in rabbits following repeated intravenous injections of bacterial pyrogens.
• To explore factors influencing pyrogen tolerance, including injection frequency, dose escalation, and cross-reactivity.

Main Methods:

• Rabbits were administered daily, semiweekly, or weekly intravenous injections of pyrogenic substances from E. typhosa, S. marcescens, and Ps. aeruginosa.
• Dose-response relationships and the effects of rest periods on tolerance were examined.
• Cross-tolerance between different bacterial pyrogens was assessed.
• The role of antipyretics and mechanically induced fever on tolerance development was investigated.

Main Results:

• Repeated daily injections led to a progressive diminution in febrile response, followed by a plateau, indicating tolerance.
• Less frequent injections resulted in less pronounced tolerance development.
• Pyrogen tolerance was rapidly lost after a 3-week rest period.
• Gradual dose escalation successfully established tolerance, enabling higher pyrogen doses without fever.
• Pre-exposure to S. marcescens or Ps. aeruginosa pyrogens reduced the febrile response to E. typhosa vaccine, suggesting cross-tolerance.
• Passive transfer of unresponsiveness was not observed.
• Antipyretic use during immunization did not impede tolerance development.
• Mechanically induced fever did not reduce responsiveness to bacterial pyrogens.

Conclusions:

• Rabbits exhibit a distinct pattern of tolerance development to bacterial pyrogens, characterized by initial adaptation and subsequent plateauing of febrile response.
• Tolerance is dose-dependent and frequency-dependent, with rapid loss upon cessation of exposure.
• Cross-tolerance exists between pyrogens from different bacterial species.
• Tolerance to pyrogens is an active process within the animal, not transferable passively.