lactoferrin and Burns

Topics: Burns; Humans; Lactoferrin; Publishing; Sepsis

Fatal infections in severely burned patients are often preceded by a decline in the production of colony-stimulating factor (CSF) and the proliferation of granulocyte-macrophage stem cells (CFU-GM), and overwhelming sepsis is often associated with leukopenia. The underlying mechanisms accounting for these granulopoietic defects are poorly understood, but the fact that postburn serum has been shown to inhibit CSF production suggests that a humoral factor or factors may play a role. Previous work has demonstrated that plasma levels of lactoferrin (LF), a known inhibitor of CSF production, are elevated following burn injury. To determine if LF is responsible for serum-mediated inhibition of CSF production, serial plasma levels of LF were measured in 18 burn patients using an enzyme-linked immunoabsorbent assay (ELISA). LF was elevated within 24 hours of injury and was associated with an absolute granulocytosis which rapidly declined, reaching a nadir at postburn days 3 through 5. Postburn serum, especially when collected during the first 24 hours following burn injury, inhibited in vitro CSF production by normal human peripheral blood mononuclear cells. Pre-incubation of postburn serum with an LF antibody restored normal CSF production. These data suggest that LF may play an important role in the regulation of postburn granulopoiesis.

Topics: Adult; Aged; Antibodies; Burns; Colony-Forming Units Assay; Colony-Stimulating Factors; Enzyme-Linked Immunosorbent Assay; Female; Granulocytes; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Macrophages; Male; Middle Aged; Neutralization Tests

The number of granulocytic stem cells (CFU-C) was measured in the peripheral blood of surviving and nonsurviving burned humans. It has been shown that the number of CFU-C in the peripheral blood of survivors increases over time and is elevated compared to the number found in normal humans. The number found in nonsurvivors, however, falls significantly in the later stages of burn injury, suggesting perhaps a defect in stem cell production and/or differentiation in patients with severe thermal injuries. The mechanism is unclear but its delineation may have an important bearing on understanding the nature of infectious complications following thermal injury.

Topics: Adult; Aged; Burns; Colony-Forming Units Assay; Granulocytes; Humans; Lactoferrin; Middle Aged; Polysaccharides, Bacterial; Prostaglandins E; Sepsis; Stem Cells

Twenty burned patients were studied (with mean body surface area burned 46.5%, mean age 25.4 years, and mean survival probability 78%), and lactoferrin, white-cells count and blood cultures were determined. Lactoferrin was detected more frequently (P less than 0.01) in the samples of patients with positive blood cultures. The role of lactoferrin in host defense mechanism and its possible function in sepsis is considered.

Topics: Adolescent; Adult; Aged; Blood; Burns; Child; Child, Preschool; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Middle Aged; Prognosis

Complement activation and neutropenia have been observed in thermally injured animals. In burn patients, granulocyte chemotaxis and morphological loss of specific granules occur. We conjectured that complement is activated in humans and, in turn, induces granulocytes to secrete lactoferrin (LF), a marker of granulocyte activation. Twenty burn patients were evaluated for absolute granulocyte count (AGC), plasma levels of anaphylatoxins (C3a, C4a, C5a), and lactoferrin. The AGC directly correlated with the extent of the burn on day 1. Similarly, plasma LF on day 1 correlated with the percent burn. Those with greater than 30% burn had plasma LF between 10 and 40 micrograms/ml (normal LF = 1.5 +/- 1.8 micrograms/ml). In five patients without further complications followed serially, plasma LF did not return to normal until 2 to 5 weeks. In all patients, there was evidence of complement activation; C4a ranged between 283 and 13,064 ng/ml and C3a between 19 and 852 ng/ml. In some patients, C5a was detectable, but the values correlated inversely with the extent of burn. On the other hand C3a and C4a levels did not correlate with the extent of burn but threefold to fivefold rises of C3a levels on days 7 and 9 predicted gram-negative sepsis. Although plasma LF did not predict sepsis, levels greater than 12 micrograms/ml on day 1 heralded the onset of neutropenia on day 3 in 60% of patients with 30% burn. Six of 20 patients developed pulmonary radiographic changes and, in five of the six, the changes occurred by day 3. Plasma LF in all six patients on day 1 was greater than 17 micrograms/ml. In two patients with greater than 50% burn, depletion of granulocyte LF was demonstrated histochemically. These studies indicate that complement is activated in burn patients, which is associated with granulocyte secretion. Measurement of plasma anaphylatoxins and LF may serve as useful aides in clinical management of these patients.

Topics: Adult; Burns; Complement Activation; Complement C3; Complement C3a; Complement C4; Complement C4a; Complement C5; Complement C5a; Female; Granulocytes; Humans; Lactoferrin; Lactoglobulins; Male