Anti-tumor necrosis factor-alpha treatment activates Borrelia burgdorferi spirochetes 4 weeks after ceftriaxone treatment in C3H/He mice.

Background: The effect of anti-tumor necrosis factor (TNF)-alpha treatment in Borrelia burgdorferi-infected and ceftriaxone-treated C3H/He mice was evaluated.

Methods: Mice were infected with B. garinii A218 or B.

Persistent joint swelling and Borrelia-specific antibodies in Borrelia garinii-infected mice after eradication of vegetative spirochetes with antibiotic treatment.

We wanted to study the pathogenesis and the long-term manifestations of Borrelia garinii infection in SJL and C3H/He mice. We report here that B. garinii A218 causes a persisting infection in these mouse strains.

Sublethal concentrations of complement can effectively opsonize Borrelia burgdorferi.

The fate of borreliae invading a human may depend on the early innate response they induce. The interactions of human complement system and neutrophils with two strains of the Lyme borreliosis spirochete Borrelia burgdorferi were studied. Borrelia burgdorferi sensu stricto B31 (resistant to a 28% concentration of normal human serum (NHS)) and Borrelia garinii Bg A218/98 (sensitive to 7% NHS) were examined.

Borrelia burgdorferi--induced oxidative burst, calcium mobilization, and phagocytosis of human neutrophils are complement dependent.

When Borrelia burgdorferi, the spirochete causing Lyme disease, is transmitted to a human, the complement system is among the first challenges facing the bacterium. Neutrophils are crucial leukocytes in the first line of host defense against bacterial infections. To investigate the role of complement in the Borrelia-induced activation of human neutrophils, oxidative burst, calcium mobilization, and phagocytosis induced by three subspecies of B.

Tube phagocytosis, a novel way for neutrophils to Phagocytize borrelia burgdorferi.

Interactions between human neutrophils and Borrelia burgdorferi, the Lyme disease spirochete, were studied by dark-field microscopy combined with video technology. A previously unrecognized mechanism for neutrophils to phagocytize the spirochete was discovered. During phagocytosis, the spirochete attaches to the neutrophil head-on, the neutrophil forms a thin tubelike protrusion around the bacterium, and the fully covered spirochete is drawn into the cell.

Unidirectional heterologous receptor desensitization between both the fMLP and C5a receptor and the IL-8 receptor.

During inflammation neutrophils receive multiple signals that are integrated, allowing a single modified response. One mechanism for this discrimination is receptor desensitization, a process whereby ligand-receptor binding is disassociated from cell activation. We examined the effect of heterologous receptor desensitization on neutrophil chemotaxis, calcium mobilization, and arachidonic acid production, using interleukin-8 (IL-8), C5a, and N-formyl-methionyl-leucyl-phenylalanine (fMLP).

Interleukin-8 is a major component of pleural liquid chemotactic activity in a rabbit model of endotoxin pleurisy.

Gram-negative endotoxin induces production of the potent chemotactic factor interleukin-8 (IL-8) in vitro; however, the importance of IL-8 in endotoxin-induced inflammation in vivo is unknown. We asked whether IL-8 is an important contributor to chemotactic activity in acute inflammatory liquids formed in response to endotoxin, and, if present, what concentrations of IL-8 antigen are generated. For these studies, we cloned and expressed rabbit recombinant IL-8 (rrIL-8), developed specific anti-rabbit IL-8 monoclonal antibodies (mAb), and then used these reagents to develop assays to detect rabbit IL-8 bioactivity and measure rabbit IL-8 antigen.

Clostridium perfringens in stool, intrapartum antibiotics and gastrointestinal signs in a neonatal intensive care unit.

In 1989, we observed in our neonatal intensive care unit (NICU), an increased number of infants with gastrointestinal signs, including five cases of necrotizing enterocolitis. Clostridium perfringens was found in 26% of newborns (n = 168) and was associated significantly with the occurrence of flatulence, distended abdomen, foul-smelling stools, diarrhea and blood in stool (all p < 0.001).

Inhibition of polymorphonuclear leucocyte functions in vivo by Yersinia enterocolitica lipopolysaccharide.

A single intravenous injection of 5 micrograms of Yersinia enterocolitica lipopolysaccharide (LPS) inhibits rabbit polymorphonuclear leucocyte (PMN) chemotaxis, enzyme secretion, and respiratory burst activation in response to partially purified rabbit C5a and leucotriene B4 (LTB4). Respiratory burst activation is also inhibited in response to platelet activating factor (PAF). In contrast, all these responses to n-formyl-methionyl-leucyl-phenylalanine (FMLP) remain unaltered.

Lack of correlation between calcium mobilization and respiratory burst activation induced by chemotactic factors in rabbit polymorphonuclear leukocytes.

Low concentrations of FMLP, partially purified rabbit C5a, leukotriene B4 and platelet activating factor induced a rapid rise of intracellular free Ca2+ in rabbit polymorphonuclear leukocytes. However, the four factors differed markedly in their ability to activate the respiratory burst. The peptides FMLP and C5a induced a single, strong chemiluminescence response whereas the lipids leukotriene B4 and platelet activating factor induced a markedly less intense response with a two-peak profile.

Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors.

To assess the mechanism and specificity of polymorphonuclear leukocyte (PMN) dysfunction induced by endotoxin, rabbits were injected intravenously with 100 micrograms of Escherichia coli endotoxin, and PMN function was studied 18 to 24 h later. Compared to PMN from normal rabbits, peripheral blood PMN from rabbits injected with endotoxin showed diminished chemotactic responsiveness to two endogenous peptides, C5a (complement) and platelet-derived growth factor, and to two endogenous lipids, leukotriene B4 and platelet-activating factor. The chemotactic response to the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), was unimpaired.

Endotoxin tolerance diminishes certain antiinflammatory effects of endotoxin.

Endotoxin (bacterial lipopolysaccharide, LPS) is paradoxically both inflammatory and antiinflammatory. A single intravenous injection of 100 micrograms Escherichia coli LPS markedly inhibits the inflammatory changes associated with cutaneous reversed passive Arthus (RPA) reactions in New Zealand white rabbits. Polymorphonuclear (PMN) leukocytes from LPS-treated rabbits exhibit diminished responsiveness in vitro to complement (C5) -derived peptides.

Complement and polymorphonuclear leukocytes do not determine the vascular permeability induced by intraocular LPS.

The intravitreous injection of an endotoxin of Escherichia coli 055:B5 (LPS; 0.1-0.5 microgram/50 microliters of saline) induces ocular inflammation in rabbits that is maximal 20-24 hours later and disappears by 4 days.

Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis.

Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 10(4) cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, cerebrospinal fluid contained neither polymorphonuclear leukocytes nor chemotactic activity.

Antiinflammatory effects of endotoxin. Inhibition of rabbit polymorphonuclear leukocyte responses to complement (C5)-derived peptides in vivo and in vitro.

Although capable of provoking a variety of inflammatory effects, endotoxin (bacterial lipopolysaccharide) paradoxically has been reported to be antiinflammatory. The authors have found that single intravenous injections of Escherichia coli endotoxin, 24 hours before challenge, inhibit almost completely the vascular permeability changes and exudation of polymorphonuclear leukocytes induced in rabbit skin by reversed passive Arthus reactions. Whereas intravenous injections of endotoxin also caused modest inhibition of the vascular permeability changes induced in rabbit skin by the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), exudation of polymorphonuclear leukocytes was unaffected.

Indomethacin inhibits arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in hamster isolated lungs.

14C-Arachidonic acid (AA, 66 nmol) was injected into the pulmonary circulation of isolated perfused hamster lungs. The metabolites were analysed from the nonrecirculating perfusion effluent, which was extracted with ethyl acetate first at pH 7.4 (to extract unmetabolized AA, metabolites of lipoxygenase and HHT) and then at pH 3.

Effects of tetraethyl lead on the activities of drug metabolizing enzymes in different tissues of the rat.

The present study describes the effects of tetraethyl lead on various drug metabolizing enzymes in different tissues of the rat. Tetraethyl lead was administered intraperitoneally to rats (250 mumol/kg) on two consecutive days. The animals were killed on day 3.