Can systemic inflammation lower albumin and raise globulins to produce a low A/G ratio?

Systemic inflammation can produce the described protein pattern, particularly during severe acute illness or sustained immune activation. Albumin and globulin results should nevertheless be interpreted with the clinical setting and more specific protein studies.

Clinical and laboratory evidence

• Albumin is a negative acute-phase protein. In bacteremia, sepsis, and trauma, circulating albumin can fall rapidly, largely because increased vascular permeability promotes transcapillary escape into the interstitial compartment. Increased catabolism, dilution, and concurrent organ disease can also contribute.
• Inflammation can raise globulin fractions. Acute-phase responses typically increase the α1 and α2 electrophoretic regions, reflecting proteins such as α1-antitrypsin, α1-acid glycoprotein, and haptoglobin.
• With persistent inflammation, broad polyclonal γ-globulin elevation may occur through increased immunoglobulin production. Lower albumin and higher globulins each reduce the albumin-to-globulin (A/G) ratio; together they make a low ratio more likely.

Mechanistic context

• Inflammatory cytokine signaling, particularly IL-6, shifts hepatic protein production toward positive acute-phase proteins, while albumin’s circulating concentration may additionally decline through capillary leak and altered distribution.
• Sustained antigenic and cytokine-driven B-cell activation, followed by plasma-cell immunoglobulin secretion, provides a mechanism for polyclonal globulin increases. The affected fraction and timing differ between acute and chronic inflammatory states.

Interpretation in practice

• A low A/G ratio is compatible with inflammation but is not diagnostic. It can result from low albumin alone, high globulins alone, or both.
• Liver dysfunction, renal or gastrointestinal protein loss, hemodilution, nutritional status, and other causes of hypoalbuminemia remain important considerations. Serum protein electrophoresis and direct immunoglobulin measurement can distinguish acute α-fraction changes or polyclonal patterns from other abnormalities.

Bottom line

• The claim is well supported: systemic inflammation can lower circulating albumin through negative acute-phase physiology and redistribution while increasing globulin fractions, thereby producing a low A/G ratio.