Role of circulating complement and polymorphonuclear leukocyte transfusion in treatment and outcome in critically ill neonates with sepsis

Cairo, Mitchell S.; Worcester, Carrie C.; Rucker, Ralph W.; Bennetts, Geni A.; Amlie, Ragnar; Perkin, Ronald M.; Anas, Nicholas; Hicks, David

doi:10.1016/s0022-3476(87)80418-3

Cited by 62 publications

(35 citation statements)

References 29 publications

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“…These deficits include decreased deformability and chemotaxis (1 9,20), defective opsonic activity and phagocytosis (21), a discrepancy between superoxide and hydroxyl radical generation (22), reduced oxidative responses in stressed newborns (23) and impaired bacterial killing in newborns stressed or concurrently infected (24). These qualitative and additional quantitative abnormalities in neonatal myeloid bone marrow precursors and circulating PMN have suggested the need for additional adjuvant therapy in the treatment of overwhelming neonatal sepsis (25).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Primes Neonatal Granulocytes for Enhanced Oxidative Metabolism and Chemotaxis

et al. 1989

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ABSTRACT. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces proliferation and differentiation of hematopoietic stem cells. Additionally, rhGM-CSF enhances the physiologic responses of adult polymorphonuclear leukocytes (PMN) especially with respect to oxidative metabolism and chemotaxis. Neonatal PMN are deficient in chemotaxis and have been demonstrated to have reduced oxidative responses in times of stress. We evaluated the priming effects of rhGM-CSF (1-100 pmol/L) on cord (neonatal) superoxide production and chemotaxis. Cord and adult PMN were incubated with 100 pmol/L rhGM-CSF (Amgen, 4 % lo7 U/ mg) for 0-120 rnin and stimulated with ~lform~l-1-methionyl-1-leucyl-phenylalanine. RhGM-CSF enhanced 02-production at all time periods with maximal priming at 60 min (147.97 f 11.14% p 5 0.006) with less, but significant enhancement at 120 rnin (116.53 f 7.92% p 5 0.05).Maximal adult PMN 02-release occurred at 120 min (190.02 f 8.71% p 5 0.003) and was more pronounced than cord PMN. RhGM-CSF (100 pmol/L x 30 rnin) incubation of cord PMN also primed for increased PMN 0 2 -release after zymosan-activated serum stimulation ( p 5 0.05) but not PMA (p = NS). Co-incubating cord PMNs with 100 pmol/L rhGM-CSF and a murine anti-human GM-CSF antibody (0-100 mcg/ml) resulted in 95% inhibition of the priming effect of rhGM-CSF enhancement of cord PMN 02-release. RhGM-CSF, primed cord PMN for enhanced chemotaxis during early incubation (5 min) with both N-formyl-1-methionyl-1-leucyl-phenylalanine M) and Escherichia coli filtrate (113.54 f 6.11% p 5 0.025 and 110.84 f 4.69% p 5 0.001), respectively, but not at 30-min or 60-min incubation. These studies suggest that rhGM-CSF similarly primes neonatal PMN like adult PMN for enhanced in vitro PMN oxidative responses and chemotaxis. (Pediatr Res 26: 395-399, 1989) Abbreviations PMN, polymorphonuclear leukocyte (bands + neutrophils) rhGM-CSF, recombinant human granulocyte-macrophage colony stimulating factor

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Primes Neonatal Granulocytes for Enhanced Oxidative Metabolism and Chemotaxis

et al. 1989

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“…In the absence of transplacentally acquired antibodies, the neonate must rely on the complement system for opsonization of invading bacterial pathogens. The importance of an intact complement system in septic neonates has been recently emphasized; in the report by Cairo et al (14), impaired complement function, as measured by an abnormally low CH50, was the single most important predictor of mortality in infected newborns.…”

Section: 78)mentioning

confidence: 99%

“…In addition, function of the newborn's complement system is also impaired and may increase the risk of infection (9)(10)(11)(12)(13). For example, Cairo et al (14) have recently shown that a low CH50, a measure of the hemolytic activity of complement, is the most significant determinant of mortality in septic newborns, regardless of gestational age.…”

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confidence: 99%

Biochemical Abnormalities of the Third Component of Complement in Neonates

Zach

Hostetter

1989

Pediatr Res

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ABSTRACT. The third component of complement, C3, is of central importance as an opsonin in the nonimmune host. Although gestational deficiencies in C3 levels are well recognized in neonates, defects in complement-mediated functions have not in every case correlated with low levels of complement proteins. Because opsonic functions of C3 are mediated through a reactive thiolester bond, we hypothesized that a biochemical dysfunction at this active site could explain the newborn's predisposition to infection, even with relatively normal C3 levels. We therefore examined the biochemical integrity of the C3 thiolester in an assay independent of all other complement proteins. As measured by ELISA, mean C3 levels from 44 neonates (24-43 wk) were significantly lower in infants < 30 wk gestational age (0.79 f 0.13 mg/mL) than in full-term newborns (1.19 +1 0.27 mg/ml, p < 0.05). Furthermore, biochemical reactivity of the thiolester bond, as measured by incorporation of the radiolabeled nucleophile, methylamine, correlated significantly with gestational age ( r = 0.45, p < 0.01). Functional C3 was defined as the product of thiolester reactivity and C3 level; 9/11 premature and 2/ 17 full-term infants had levels of functional C3 which were less than 50% of the adult norm. Structural analysis of neonatal C3 revealed the two-chain structure in all neonates; four neonates had an additional band at 205 kD which may represent an impairment in posttranslational processing of a precursor molecule. We conclude that defects in thiolester reactivity may constitute a newly identified mechanism for the newborn's susceptibility to infection. (Pediatr Res 26: 116-120, 1989) Abbreviations PAS, pooled adult serum CH3NH2, methylamine Sepsis is a leading cause of morbidity and mortality in neonates, with premature infants affected more frequently than fullterm newborns (I). This predisposition to infection is ascribable, at least in part, to age-related defects in host defense (2, 3). Primary among humoral defenses are the complement proteins, which serve as opsonins for common neonatal pathogens such as the group B Streptococcus or the K1 capsular serotype of Escherichia coli (4,5).

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“…[1][2][3] Neutropenia is a clinical feature of GBS sepsis that has been associated with poor outcome. 36 Cairo et al 37,38 investigated the potential role of leukocyte transfusions to treat infants with neonatal sepsis. The use of CSFs as another means of correcting sepsis-associated neutropenia has been investigated.…”

Section: Discussionmentioning

confidence: 99%