This study sought to determine the circulating levels of cytokines and their respective
endogenous modulators in patients with congestive heart failure of variable severity.
Activation of immune elements localized in the heart or periphery, or both, may promote
release of cytokines in patients with congestive heart failure. Although an increased
circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor
type II (sTNF-RII) is well documented, less is known about other cytokines (i.e.,
interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and
their soluble receptor/receptor antagonists).
Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist
(IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha
were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems)
in 80 patients with congestive heart failure due to coronary artery disease or hypertension.
The severity of their symptoms, which ranged from New York Heart Association functional
class I to IV, was confirmed by measurement of peak oxygen consumption.
The percentage of patients with elevated levels of cytokines and their corresponding
soluble receptor/receptor antagonists significantly increased with functional class.
For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble
receptor/receptor antagonists was higher than that of patients with elevated levels
of the cytokine itself. For IL-6, the percentage of patients with elevated levels
of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6.
All but two patients had undetectable levels of IL-2, and all but seven had levels
of IL-2-sR within a normal range.
In patients with congestive heart failure, circulating levels of cytokines increased
with the severity of symptoms. In these patients, circulating levels of sTNF-RII and
IL-1-Ra are more sensitive markers of immune activation than are circulating levels
of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated
when congestive heart failure is due to coronary artery disease or hypertension.