This administrative supplement request to purchase equipment is being submitted in response to PA-18-591 (NIGMS Program of Administrative Supplements for Equipment). My currently funded R01 GM122934 is the parent award for this supplemental request. I am requesting funding for a Mesoscale QuickPlex SQ 120. The critically ill patient frequently develops a complex disease spectrum that may include systemic inflammatory response syndrome, sepsis syndrome, septic shock and/or multiple organ dysfunction syndrome. In the United States ~951,000 patients/year develop sepsis with approximately half of these patients in the ICU. The overall mortality rate is 28.6%. Those patients that survive the initial septic event may ultimately succumb to widespread organ dysfunction due to ongoing immune dysfunction. It is well accepted that sepsis causes suppression of the immune system, and that sepsis-induced immunoparalysis predisposes the critically ill patient to secondary infections. Secondary fungal infections are one of the most serious, as they are difficult to diagnose and treat. Attempts at developing effective therapies to prevent or treat sepsis and its associated immunosuppression have proven to be exceedingly difficult. In fact, no drugs are currently approved by the FDA for the management of sepsis. A very important aspect of this research is to establish the impact of sepsis on leukocytes and innate immune parameters in sepsis. To achieve this goal, we will critically analyze cytokines, chemokines and biomarkers from sepsis patients. This will require a detection sensitivity and dynamic range that is far beyond our current capabilities. The Mesoscale QuickPlex SQ 120 that is requested in this supplement will fill this critical and unmet need. In addition, the increase capabilities of the SQ 120 will allow us to more critically evaluate our working hypotheses.
. Sepsis, septic shock and multi-organ failure are major clinical problems in the United States. Despite years of intensive research, there is still much that we do not know about the mechanisms of these devastating diseases. Attempts at developing effective therapies for sepsis/septic shock and multi-organ failure have proven to be exceedingly difficult. One of our goals is to discover new and novel targets for therapy to prevent and/or treat sepsis. To accomplish that goal we are attempting to understand the cellular and molecular mechanisms of sepsis. To that end, we are requesting supplemental funds for a new piece of equipment that will allow us to characterize the immune response of human cells during sepsis.