Leukocytosis is a common feature of inflammatory reactions, especially those induced by bacterial infections. The leukocyte count usually climbs to 15,000 or 20,000 cells/mL, but sometimes it may reach extraordinarily high levels of 40,000 to 100,000 cells/mL. These extreme elevations are referred to as leukemoid reactions, because they are similar to (and must be distinguished from) the white cell counts observed in leukemia. The leukocytosis occurs initially because of accelerated release of cells from the bone marrow postmitotic reserve pool (caused by cytokines, including TNF and IL-1) and is therefore associated with a rise in the number of more immature neutrophils in the blood, referred to as a shift to the left. Prolonged infection also induces proliferation of precursors in the bone marrow, caused by increased production of colony-stimulating factors (CSFs). Thus, if inflammation is sustained the bone marrow output of leukocytes increases, an effect that usually more than conpensates for the loss of these cells in the inflammatory reaction. (See also the discussion of leukocytosis in Chapter 12.) Most bacterial infections induce an increase in the blood neutrophil count, called neutrophilia. Viral infections, such as infectious mononucleosis, mumps, and German measles, cause an absolute increase in the number of lymphocytes (lymphocytosis). In some allergies and parasitic infestations, there is an increase in the number of blood eosinophils, creating an eosinophilia. Certain infections (typhoid fever and infections caused by some viruses, rickettsiae, and certain protozoa) are associated with a decreased number of circulating white cells (leukopenia).
Other manifestations of the acute-phase response include increased heart rate and blood pressure; decreased sweating, mainly because of redirection of blood flow from cutaneous to deep vascular beds, to minimize heat loss through the skin; rigors (shivering), chills (search for warmth), anorexia, somnolence, and malaise, probably because of the actions of cytokines on brain cells.
In severe bacterial infections (sepsis), the large amounts of bacteria and their products in the blood stimulate the production of enormous quantities of several cytokines, notably TNF and IL-1. High blood levels of cytokines cause widespread clinical and pathologic abnormalities such as disseminated intravascular coagulation, hypotensive shock, and metabolic disturbances including insulin resistance and hyperglycemia. This clinical triad is known as septic shock; it is discussed in more detail in Chapter 4. A syndrome similar to septic shock may occur as a complication of noninfectious disorders, such as severe burns, trauma, pancreatitis, and other serious conditions. Collectively these reactions are called systemic inflammatory response syndrome (SIRS).
We next consider the process of repair, which is a healing response to tissue destruction resulting from inflammation or other causes.
Fever: Cytokines (TNF, IL-1) stimulate production of PGs in hypothalamus
Production of acute-phase proteins: C-reactive protein, others; synthesis stimulated by cytokines (IL-6, others) acting on liver cells
Leukocytosis: Cytokines (CSFs) stimulate production of leukocytes from precursors in the bone marrow
In some severe infections, septic shock: Fall in blood pressure, disseminated intravascular coagulation, metabolic abnormalities; induced by high levels of TNF and other cytokines
Overview of Tissue Repair
Critical to the survival of an organism is the ability to repair the damage caused by toxic insults and inflammation. In fact, the inflammatory response to microbes and injured tissues not only serves to eliminate these dangers but also sets into motion the process of repair.