SGp130 in Septic Shock: Not a Current Treatment Option
SGp130 (soluble glycoprotein 130) is not an established or recommended therapy for septic shock and does not appear in any major sepsis guidelines, including the most recent Surviving Sepsis Campaign guidelines. 1
What is SGp130?
SGp130 is a naturally occurring soluble receptor that selectively blocks IL-6 trans-signaling by binding the IL-6/soluble IL-6 receptor complex, preventing it from activating cells through the gp130 pathway. 2
Current Evidence Status
Experimental Research Only
- Animal studies show promise but no human trials exist for sepsis treatment. In murine cecal ligation and puncture (CLP) sepsis models, sgp130Fc (a fusion protein) increased survival from 45% to 100% when given before sepsis, and from 45% to 80% when given 24 hours after sepsis onset. 2
- The mechanism appears to involve prevention of intestinal epithelial cell apoptosis, which was not achieved with complete IL-6 blockade using anti-IL-6 antibodies. 2
- Selective IL-6 trans-signaling blockade with sgp130 may preserve beneficial "classic" IL-6 signaling while blocking harmful trans-signaling effects. 2
Why It's Not Used Clinically
- No human clinical trials have been conducted for septic shock. 2
- The Surviving Sepsis Campaign guidelines (2012,2016,2017) make no mention of sgp130 or IL-6 trans-signaling blockade as a therapeutic option. 1
- Myeloid cell gp130 signaling is actually protective in sepsis, promoting M2 macrophage polarization and anti-inflammatory responses—complete blockade worsens outcomes. 3
Current Standard of Care for Septic Shock
Instead of experimental immunomodulatory agents, focus on evidence-based interventions:
Immediate Resuscitation (First 3 Hours)
- Administer at least 30 mL/kg of crystalloid solution (balanced crystalloids or normal saline preferred over colloids). 1, 4
- Initiate vasopressors if hypotension persists despite fluids, targeting mean arterial pressure ≥65 mmHg with norepinephrine as first-line agent. 1, 4
- Obtain blood cultures before antibiotics and administer broad-spectrum antimicrobials within 1 hour of sepsis recognition. 1
Avoid Harmful Interventions
- Do not use hydroxyethyl starch (HES) in septic patients—it increases mortality and acute kidney injury without benefit. 5
- Balanced crystalloids (Ringer's lactate, Plasma-Lyte) are preferred over normal saline to avoid hyperchloremic acidosis. 5, 6
Clinical Bottom Line
SGp130 remains an investigational agent with no role in current septic shock management. Adhere to Surviving Sepsis Campaign guidelines focusing on early fluid resuscitation, appropriate antimicrobials, source control, and vasopressor support. 1, 4