Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway

Area of Science:

• Immunology
• Physiology

Background:

• Therapeutic hypothermia improves neurological outcomes in ischemia-reperfusion injury.
• Antibody-initiated complement activation contributes to ischemia-reperfusion injury.
• The effect of hypothermia on complement activation remains unclear.

Purpose of the Study:

• To measure the independent effect of temperature on complement activation.
• To examine the relationship between clinical hypothermia (31-33°C) and complement activation.

Main Methods:

• Assayed complement activation using antibody-sensitized erythrocytes from 0-41°C.
• Quantified complement pathway components via ELISA, Western blot, and dot blot.
• Utilized Peptide Inhibitor of complement C1 (PIC1) to inhibit C1 activation.

Main Results:

• Complement activation and cell lysis increased 2-fold at 31°C compared to 37°C.
• C4, C3, and C5 activation significantly increased at hypothermia temperatures.
• Increased C1q binding, not C1s activity, mediated enhanced classical pathway activation at lower temperatures.

Conclusions:

• Therapeutic hypothermia temperatures enhance antibody-initiated complement activation and cell destruction.
• This suggests hypothermia's benefits might be mediated by other mechanisms.
• Hypothermia-enhanced complement activation may attenuate therapeutic benefits in diseases involving this pathway.