Interest: Cytokine control of immune
responses after injury
Previous work has focused on the effects of
injury on young males, and mechanisms and therapeutic
interventions were tested exclusively in that
population. Research in the Kovacs' laboratory
focuses on how age, gender, and alcohol exposure
affect inflammation and immunity after injury.
1) Studies are exploring the mechanisms by which
estrogen and testosterone modulate macrophage
and lymphocyte function after injury. In these
studies, hormone regulation of production of
pro- and anti-inflammatory cytokines, including
tumor necrosis factor α, interleukin-1,
interleukin-6, interleukin-10, and transforming
growth factor β, is being examined. Further
investigation includes testing the therapeutic
efficacy of gonadal steroid hormones and hormone
receptor antagonists in combination with anti-cytokine
antibodies to improve immune responses. 2) Advanced
age is associated with a weakened immune system
and alterations in glucocorticoid and gonadal
steroid hormone levels. Therefore, affects of
the aging endocrine system on cell-mediated
immune responses after injury are being investigated.
By giving hormone supplementation or receptor
antagonists, it should be possible to restore
the hormone milieu to that of a young adult
and improve immunity. 3) Neither moderate ethanol
exposure nor minor injuries have prolonged effects
on young adults, but together they can result
in marked increases in morbidity and mortality.
The combined insult affects multiple organ systems,
including the lung, liver, and skin, as well
as the immune system. Current studies in the
Kovacs laboratory are determining mechanisms
by which alcohol exposure affects leukocyte
function after injury and whether cytokine and
anti-cytokine treatment regimens can be used
to improve these responses.
