Neurohormonal host defense in endotoxin shock

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Lipopolysaccharide (LPS) from gram-negative bacteria triggers immune responses, potentially causing lethal shock in mammals.
• LPS elicits varied responses across species, from minimal in fish to lethal coagulation in horseshoe crabs.
• The mammalian response to LPS evolved into the acute-phase response (APR), involving complex immune, neuroendocrine, and metabolic changes.

Purpose of the Study:

• To elucidate the mechanisms of LPS-induced acute-phase response (APR).
• To explore the role of LPS-binding proteins (LBP) and other receptors in LPS recognition and immune activation.
• To investigate the hypothesis that intestinal LPS amplifies APR for host defense and healing.

Main Methods:

• The study reviews existing evidence on LPS interactions with immune cells and the induction of APR.
• It discusses the involvement of specific receptors like CD14, CD18, and an 80-kDa receptor in LPS signaling.
• The role of liver-produced acute-phase proteins, including LBP, C-reactive protein, and complement components, is examined.

Main Results:

• LPS activates monocytes-macrophages and granulocytes via LBP and CD14, and directly through other receptors.
• The liver produces numerous acute-phase proteins, such as C-reactive protein and fibrinogen, during APR.
• Endotoxin tolerance, induced by subtoxic LPS doses, enhances resistance to infections and insults.

Conclusions:

• APR is an efficient, albeit non-specific, host defense mechanism against infections and tissue injury when specific immunity fails.
• Neuroimmunoregulation converts the immune system to a rapid APR during emergencies.
• Intestinal LPS is hypothesized to amplify APR, contributing to host defense, regeneration, and healing.