Role of cytokines in the modulation of neutrophil chemotaxis in localized juvenile periodontitis

Abstract

Decreased neutrophil chemotaxis has been implicated in the pathophysiology of the disease, localized juvenile periodontitis (LJP). The biological basis for the altered neutrophil function in LJP has been suggested to be an intrinsic cellular defect, involving a decrease in the number of N-formyl-methionyl-leucyl-phenylalanine (FMLP) receptors on the cell surface. We have investigated the relative contribution of serum-borne factors in the modulation of neutrophil functions in LJP, in a large population of LJP patients and healthy control subjects (HS). Treatment of HS-neutrophils with LJP-sera, resulted in a decreased neutrophil chemotactic response, and down regulation of FMLP receptors on the cell surface. Pretreatment of LJP-sera with anti-TNF and anti-IL-1 antibodies effectively, although incompletely, neutralized the ability of LJP-sera to modulate chemotaxis and FMLP receptor levels in HS-neutrophils. The changes induced by LJP sera were specific and sustained and could not be reversed by placing LJP-serum treated neutrophils in HS-serum. Sera obtained from HS and patients with adult periodontitis (AP), both of which exhibit normal chemotaxis, and patients with clinically diagnosed LJP with normal neutrophil chemotaxis (LJP-nctx) did not modulate HS neutrophil chemotaxis or FMLP receptors. Furthermore, recombinant human TNF-alpha, rhIL-1 alpha and rhIL-1 beta, at very low concentrations (15 pg/ml to 150 pg/ml), modulated the chemotactic response as well as FMLP receptor numbers on HS-neutrophils, in a manner similar to those observed in LJP. The present findings demonstrate that the biologic basis for the altered neutrophil function may not be an intrinsic cellular defect in neutrophils, but at least in part due to quantitatively small but biologically significant elevations in the levels of TNF-alpha and IL-1 in the serum.

Polymorphisms Within the IL‐1 Gene Cluster: Effects on Cytokine Profiles in Peripheral Blood and Whole Blood Cell Cultures of Patients With Aggressive Periodontitis, Juvenile Idiopathic Arthritis, and Rheumatoid Arthritis

“…Altered neutrophil function in LAgP has been discussed extensively since the 1970s 50 . Sera from LAgP patients altered the function of normal neutrophils: an effect that may be neutralized by anti‐TNF and anti–IL‐1 antibodies 51,52 . An interesting perspective of the present study would be to investigate if IL‐1 polymorphisms are associated with functions of neutrophils in the LAgP patients.…”

Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients

“…8,9 The etiological basis for altered chemotaxis remains unknown, although both innate genetic and acquired anomalies have been proposed. 10,11 Alterations of two codons, one in the second transmembrane domain (c.329T4C/p.F110S) and one in the second intracellular loop (c.378C4G/p.C126W) of the fMLP receptor, have been reported to be significantly associated with a localized form of AP in African American patients. 12 Gwinn et al 12 reported that the mutant variant of either one or both single nucleotide polymorphisms (SNPs) (c.329T4C and c.378C4G) are present in 29 of 30 African-American patients with a localized form of AP previously called localized juvenile periodontitis.…”

Decreased phagocytic function in neutrophils and monocytes from peripheral blood in periodontal disease

“…Depression of the chemotactic response in patients with localized aggressive periodontitis may not be an abnormality associated with the cell, but rather a consequence of the elevation of the serum concentration of cytokines produced during the host-parasite interaction. The TNF-alpha and IL-1 cytokines may cause a reduction in chemotactic receptors 1 . However, increased local production of cytokines in response to pathogens in the periodontium may result in bone loss and tissue damage typically observed in more severe forms of periodontitis 10,30 .…”

“…In addition to the local effects, the bacterial virulence factors and inflammatory mediators arising from this parasite-host interaction may create and sustain a chronic systemic inflammatory process in the bloodstream 17 . In the most aggressive forms of periodontal disease, the role played by the elevated serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) has been considered partly responsible for altering the neutrophil function 1 . In addition, new perspectives have indicated that periodontitis occurs as a hyperactive immune/inflammatory response to the specific bacteria of plaque in predisposed individuals, involving the excessive generation of oxygen radicals and the release of proteases 14 .…”