USA Surgery Today

In the early twentieth century, Ehrlich and Metchnikoff were awarded Nobel prizes for recognizing the two basic components of the immune system: the humoral and cellular elements. In subsequent years, only incremental progress was made in understanding their complex and intricate interactions.

During the last decade, however, modern molecular and cell biology techniques have yielded an enormous amount of data detailing the specific components of the immune system and the regulation of the immune or inflammatory response. For instance, redness (rubor), edema (tumor), heat (calor), and pain (dolor) were recognized as the cardinal signs of inflammation more than 2,000 years ago. We now understand that these clinical manifestations are the result of vasodilation with enhanced local blood flow, which causes redness and heat, and increased microvascular permeability, which leads to edema. Extravasation of plasma proteins and leukocyte recruitment to the site of injury generate pain.

The distinction between an efficient host defense and pathological injury to host tissues can be extremely narrow. Unchecked, exuberant, or misdirected inflammatory responses can lead or contribute to systemic diseases. Indeed, dysregulated inflammatory responses play important roles in many contemporary pediatric surgical diseases, including sepsis, necrotizing enterocolitis, and meningitis, to name a few. The potential for endogenous inflammatory injury was first recognized when investigators discovered that serum sickness resulted from antigen-antibody mediated tissue injury in the host. Subsequently, the fundamental importance of acute inflammation and its role in diverse diseases such as atherosclerosis, arthritis, acute respiratory distress syndrome (ARDS), multiorgan failure syndrome, compensatory antiinflammatory response syndrome, chronic lung disease, trauma, thermal injury, acute pancreatitis, ischemia-reperfusion injury, sepsis, and transplant rejection was demonstrated. More recently, the widespread use of antimicrobial agents has helped demonstrate that stimuli other than microbes can evoke a systemic inflammatory response. For instance, ARDS may result from a systemic inflammatory response to tissue injury without overt evidence of infection.