- Ebb phase:
- First 6 to 24 hours to 48 hours:
- “Shock, conserve”
- Characterize by:
- Hypometabolism
- ↓O₂ consumption
- Relative hypothermia
- Neuroendocrine surge:
- Catecholamines
- Cortisol
- Glucagon
- The innate immune system is triggered:
- Early TNF-α / IL-1 release:
- Begins the inflammatory cascade / response PMC+1
- Early TNF-α / IL-1 release:
- First 6 to 24 hours to 48 hours:
- Flow phase:
- Catabolic sub-phase:
- From days ~ 1 to 7:
- “Hypermetabolism, mobilize”
- From days ~ 1 to 7:
- Characterize by:
- ↑O₂ consumption
- Hyperglycemia
- Insulin resistance
- Proteolysis
- TNF-α and IL-1 drive the early wave:
- Rapidly followed by IL-6:
- Acute-phase switch
- IL-8:
- Neutrophil recruitment (PMN chemotaxis)
- Angiogenesis
- Counter-regulators like IL-10:
- To prevent runaway inflammation
- Rapidly followed by IL-6:
- Clinically corresponds to SIRS:
- An anti-inflammatory counter-swing (CARS):
- Follows and may blend into MARS in severe injury PubMed+1
- An anti-inflammatory counter-swing (CARS):
- Catabolic sub-phase:
- Flow phase:
- Anabolic / Recovery sub-phase:
- Last weeks
- Characterize by:
- Gradual resolution of catabolism:
- As inflammation recedes and tissue repair predominates
- Cytokine tone shifts toward regulation and remodeling:
- Persistent but lower IL-6:
- More IL-10 / TGF-β signals ScienceDirect
- Persistent but lower IL-6:
- Gradual resolution of catabolism:
- Anabolic / Recovery sub-phase:
- Conceptual arc:
- TNF-α / IL-1 ignite the response → IL-6 flips on the acute-phase program → IL-8 pulls in neutrophils (and supports angiogenesis) → IL-10 tempers the fire
- In severe trauma, this oscillates between SIRS → CARS (sometimes MARS), tracking clinical risk for infection or organ failurePubMed+1
- Practical pearls you can teach on rounds:
- CRP is an IL-6 barometer:
- Rising CRP tracks the IL-6–driven hepatic response more than bacterial growth per se PubMed
- Fever mechanics:
- IL-1 / TNF → PGE₂ in the hypothalamus:
- Antipyretics reduce PGE₂ synthesis (COX inhibition) PMC
- IL-1 / TNF → PGE₂ in the hypothalamus:
- Atelectasis ≠ fever:
- The long-taught notion that postoperative atelectasis causes fever isn’t supported by clinical data:
- Early fevers are cytokine-mediated inflammation from surgical injury unless another source is found PubMed+1
- The long-taught notion that postoperative atelectasis causes fever isn’t supported by clinical data:
- CRP is an IL-6 barometer:
- Summary (link cytokines to phases):
- Ebb (0 to 24 hours ):
- Catecholamines / cortisol ↑
- TNF-α / IL-1 spark local and systemic inflammation PMC
- Flow:
- Catabolic (days 1 to 7):
- IL-6 → CRP / SAA
- IL-8 → neutrophil recruitment / angiogenesis
- Persistent SIRS risks early MOF
- Rising IL-10 signals CARS BioMed Central+1
- Flow:
- Anabolic (weeks):
- Inflammation resolves
- IL-10 / TGF-β tone dominates
- Net protein balance turns positive with rehab / nutrition ScienceDirect
- Anabolic (weeks):
- Catabolic (days 1 to 7):
- Ebb (0 to 24 hours ):
- References:
- Ebb/flow framework: Cuthbertson/Wilmore lineage and modern updates. PMC+1
- TNF-α endothelial activation/adhesion: Parameswaran & Patial. PMC
- IL-1 → PGE₂ fever (EP3 in POA): Blomqvist et al. PMC
- IL-6 drives CRP/SAA (human hepatocytes): Castell et al.; Sack et al. PubMed+1
- IL-8 neutrophil chemotaxis/angiogenesis: Cambier et al.; Koch et al. Nature+1
- IL-10 anti-inflammatory: Schulte et al. PMC
- SIRS → CARS model after trauma: Lenz et al.; Bone RC. PubMed+1
- Atelectasis–fever myth: Mavros et al.; Stein et al.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 