Year 2022,
Volume: 12 Issue: 2, 294 - 301, 30.06.2022
Cemalettin Demir
,
Yasemin Baranoğlu Kılınç
,
Erkan Kılınç
Project Number
2019.08.02.1415
References
- [1] Di H, He Q, Liao Y, Kalionis B, Tai X. The role of inflammatory
cytokines in the pathogenesis of cerebral palsy. Gynecol
Obstet (Sunnyvale) 2016; 6(2): 1-7.
- [2] Bennet L, Dhillon S, Lear CA, van den Heuij L, King V, Dean
JM, Wassink G, Davidson JO, Gunn AJ. Chronic inflammation
and impaired development of the preterm brain. J Reprod
Immunol 2018; 125:45-55.
- [3] Magalhães RC, Moreira JM, Lauar AO, da Silva AAS, Teixeira AL,
E Silva ACS. Inflammatory biomarkers in children with cerebral
palsy: A systematic review. Res Dev Disabil 2019; 95:1-13.
- [4] Varner MW, Marshall NE, Rouse DJ, Jablonski KA, Leveno KJ,
Reddy UM, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Thorp
JM, Malone FD, Carpenter M, O’Sullivan MJ, Peaceman AM,
Hankins GD, Dudley DJ, Caritis SN. The association of cord
serum cytokines with neurodevelopmental outcomes. Am J
Perinatol 2015; 30(2):115-122.
- [5] Tsukimori K, Komatsu H, Yoshimura T, Hikino S, Hara T, Wake
N, Nakano H. Increased inflammatory markers are associated
with early periventricular leukomalacia. Dev Med Child Neurol
2007; 49(8):587-590.
- [6] Lin CY, Chang YC, Wang ST, Lee TY, Lin CF, Huang CC. Altered
inflammatory responses in preterm children with cerebral
palsy. Ann Neurol 2010; 68(2):204-212.
- [7] Hagberg H, Mallard C, Ferriero DM, Vannucci SJ, Levison SW,
Vexler ZS, Gressens P. The role of inflammation in perinatal
brain injury. Nat Rev Neurol 2015;11(4):192-208.
- [8] Wu J, Li X. Plasma tumor necrosis factor-alpha (TNF-α) levels
correlate with disease severity in spastic diplegia, triplegia,
and quadriplegia in children with cerebral palsy. Med Sci
Monit 2015; 21: 3868-3874.
- [9] Dommergues MA, Patkai J, Renauld JC, Evrard P, Gressens
P. Proinflammatory cytokines and interleukin-9 exacerbate
excitotoxic lesions of the newborn murine neopallium. Ann
Neurol. 2000; 47(1):54-63.
- [10] Patkai J, Mesples B, Dommergues MA, Fromont G, Thornton
EM, Renauld JC, Evrard P, Gressens P. Deleterious effects of
IL-9–activated mast cells and neuroprotection by antihistamine
drugs in the developing mouse brain. Pediatr Res 2001; 50(2):
222-230.
- [11] Adlinolfi M. Infectious diseases in pregnancy, cytokines and
neurological impairment: an hypothesis. Dev Med Child
Neurol 1993; 35(6): 549-553.
- [12] Khaksari M, Abbasloo E, Dehghan F, Soltani Z, Asadikaram G.
The brain cytokine levels are modulated by estrogen following
traumatic brain injury: Which estrogen receptor serves as
modulator? Int Immunopharmacol 2015; 28(1): 279-287.
- [13] Camire RB, Beaulac HJ, Willis CL. Transitory loss of glia and
the subsequent modulation in inflammatory cytokines/
chemokines regulate paracellular claudin-5 expression in
endothelial cells. J Neuroimmunol. 2015; 284: 57-66.
- [14] Nelson KB, Blair E. Prenatal factors in singletons with cerebral
palsy born at or near term. N Engl J Med 2015; 373(10): 946-
953.
- [15] Armstrong-Wells J, Donnelly M, Post MD, Manco-Johnson MJ,
Winn VD, Sébire G. Inflammatory predictors of neurologic
disability after preterm premature rupture of membranes. Am
J Obstet Gynecol 2015; 212(2): 1-17.
- [16] Nelson KB, Dambrosia JM, Grether JK, Phillips TM. Neonatal
cytokines and coagulation factors in children with cerebral
palsy. Ann Neurol 1998; 44(4): 666-675.
- [17] Foster-Barber A, Dickens B, Ferriero DM. Human perinatal
asphyxia: correlation of neonatal cytokines with MRI and
outcome. Dev Neurosci 2001; 23(3): 213-218.
- [18] Leviton A. Preterm birth and cerebral palsy: is tumor necrosis
factor the missing link? Dev Med Child Neurol. 1993; 35(6):
553-558.
- [19] Zaitsu M, Narita S, Lambert KC, Grady JJ, Estes DM, Curran
EM, Brooks EG, Watson CS, Goldblum RM, Midoro-Horiuti
T. Estradiol activates mast cells via a non-genomic estrogen
receptor-alpha and calcium influx. Mol Immunol. 2007;
44(8):1977-1985.
- [20] Moon TC, Befus AD, Kulka M. Mast cell mediators: their
differential release and the secretory pathways involved. Front
Immunol 2014; 14(5): 1-18.
- [21] Theoharides TC. Neuroendocrinology of mast cells: Challenges
and controversies. Exp Dermatol 2017; 26(9): 751-759.
[22] Koyuncu Irmak D, Kilinc E, Tore F. Shared fate of meningeal
mast cells and sensory neurons in migraine. Front Cell Neurosci
2019; 13(136): 1-10.
- [23] Kilinc E, Tore F, Dagistan Y, Bugdayci G. Thymoquinone inhibits
neurogenic inflammation underlying migraine through
modulation of calcitonin gene-related peptide release and
stabilization of meningeal mast cells in glyceryltrinitrate-
induced migraine model in rats. Inflammation 2020; 43(1):264-273.
Increased Systemic Inflammatory Response with Mast Cell Activation In Elder Children With Cerebral Palsy
Year 2022,
Volume: 12 Issue: 2, 294 - 301, 30.06.2022
Cemalettin Demir
,
Yasemin Baranoğlu Kılınç
,
Erkan Kılınç
Abstract
Objective: Increased systemic inflammatory response during intrauterine period or period before the age of 3 is associated with cerebral palsy (CP) pathogenesis; however, effects of inflammatory processes involving mast cell activation in elder children with CP remain unclear. We aimed to investigate the role of mast cells and proinflammatory cytokines in children with CP at 3-18 years of age.
Methods: In this cross-sectional study, venous blood samples were obtained from 30 volunteers with CP and 26 healthy volunteers at 3-18 years of age. Plasma levels of proinflammatory cytokines (IL-1β, IL-6 and IL-9) and mast cell biomarkers (histamine and tryptase beta-2) were determined using ELISA.
Results: IL-1β, IL-6 and histamine levels were higher in individuals with CP compared to healthy controls. Likewise, IL-1β, IL-6, IL-9 and histamine levels were higher in the female patients with CP compared to the male patients, and in the female patients in adolescence compared to the female patients in pre-adolescence.
Conclusion: Our findings indicate that the increased inflammatory response contributes to the pathogenesis of the disease in children with CP who are older than 2 years of age. Moreover the increased inflammatory response is more effective in female patients than in male patients, suggesting that there may be a gender difference in CP. Additionally mast cell activation contributes to the exacerbation of systemic inflammatory response in children with CP at 3-18 years of age.
Supporting Institution
Bolu Abant Izzet Baysal University Scientific Research Fund
Project Number
2019.08.02.1415
Thanks
This study was supported by Bolu Abant Izzet Baysal University Scientific Research Fund (Grant-number: 2019.08.02.1415).
References
- [1] Di H, He Q, Liao Y, Kalionis B, Tai X. The role of inflammatory
cytokines in the pathogenesis of cerebral palsy. Gynecol
Obstet (Sunnyvale) 2016; 6(2): 1-7.
- [2] Bennet L, Dhillon S, Lear CA, van den Heuij L, King V, Dean
JM, Wassink G, Davidson JO, Gunn AJ. Chronic inflammation
and impaired development of the preterm brain. J Reprod
Immunol 2018; 125:45-55.
- [3] Magalhães RC, Moreira JM, Lauar AO, da Silva AAS, Teixeira AL,
E Silva ACS. Inflammatory biomarkers in children with cerebral
palsy: A systematic review. Res Dev Disabil 2019; 95:1-13.
- [4] Varner MW, Marshall NE, Rouse DJ, Jablonski KA, Leveno KJ,
Reddy UM, Mercer BM, Iams JD, Wapner RJ, Sorokin Y, Thorp
JM, Malone FD, Carpenter M, O’Sullivan MJ, Peaceman AM,
Hankins GD, Dudley DJ, Caritis SN. The association of cord
serum cytokines with neurodevelopmental outcomes. Am J
Perinatol 2015; 30(2):115-122.
- [5] Tsukimori K, Komatsu H, Yoshimura T, Hikino S, Hara T, Wake
N, Nakano H. Increased inflammatory markers are associated
with early periventricular leukomalacia. Dev Med Child Neurol
2007; 49(8):587-590.
- [6] Lin CY, Chang YC, Wang ST, Lee TY, Lin CF, Huang CC. Altered
inflammatory responses in preterm children with cerebral
palsy. Ann Neurol 2010; 68(2):204-212.
- [7] Hagberg H, Mallard C, Ferriero DM, Vannucci SJ, Levison SW,
Vexler ZS, Gressens P. The role of inflammation in perinatal
brain injury. Nat Rev Neurol 2015;11(4):192-208.
- [8] Wu J, Li X. Plasma tumor necrosis factor-alpha (TNF-α) levels
correlate with disease severity in spastic diplegia, triplegia,
and quadriplegia in children with cerebral palsy. Med Sci
Monit 2015; 21: 3868-3874.
- [9] Dommergues MA, Patkai J, Renauld JC, Evrard P, Gressens
P. Proinflammatory cytokines and interleukin-9 exacerbate
excitotoxic lesions of the newborn murine neopallium. Ann
Neurol. 2000; 47(1):54-63.
- [10] Patkai J, Mesples B, Dommergues MA, Fromont G, Thornton
EM, Renauld JC, Evrard P, Gressens P. Deleterious effects of
IL-9–activated mast cells and neuroprotection by antihistamine
drugs in the developing mouse brain. Pediatr Res 2001; 50(2):
222-230.
- [11] Adlinolfi M. Infectious diseases in pregnancy, cytokines and
neurological impairment: an hypothesis. Dev Med Child
Neurol 1993; 35(6): 549-553.
- [12] Khaksari M, Abbasloo E, Dehghan F, Soltani Z, Asadikaram G.
The brain cytokine levels are modulated by estrogen following
traumatic brain injury: Which estrogen receptor serves as
modulator? Int Immunopharmacol 2015; 28(1): 279-287.
- [13] Camire RB, Beaulac HJ, Willis CL. Transitory loss of glia and
the subsequent modulation in inflammatory cytokines/
chemokines regulate paracellular claudin-5 expression in
endothelial cells. J Neuroimmunol. 2015; 284: 57-66.
- [14] Nelson KB, Blair E. Prenatal factors in singletons with cerebral
palsy born at or near term. N Engl J Med 2015; 373(10): 946-
953.
- [15] Armstrong-Wells J, Donnelly M, Post MD, Manco-Johnson MJ,
Winn VD, Sébire G. Inflammatory predictors of neurologic
disability after preterm premature rupture of membranes. Am
J Obstet Gynecol 2015; 212(2): 1-17.
- [16] Nelson KB, Dambrosia JM, Grether JK, Phillips TM. Neonatal
cytokines and coagulation factors in children with cerebral
palsy. Ann Neurol 1998; 44(4): 666-675.
- [17] Foster-Barber A, Dickens B, Ferriero DM. Human perinatal
asphyxia: correlation of neonatal cytokines with MRI and
outcome. Dev Neurosci 2001; 23(3): 213-218.
- [18] Leviton A. Preterm birth and cerebral palsy: is tumor necrosis
factor the missing link? Dev Med Child Neurol. 1993; 35(6):
553-558.
- [19] Zaitsu M, Narita S, Lambert KC, Grady JJ, Estes DM, Curran
EM, Brooks EG, Watson CS, Goldblum RM, Midoro-Horiuti
T. Estradiol activates mast cells via a non-genomic estrogen
receptor-alpha and calcium influx. Mol Immunol. 2007;
44(8):1977-1985.
- [20] Moon TC, Befus AD, Kulka M. Mast cell mediators: their
differential release and the secretory pathways involved. Front
Immunol 2014; 14(5): 1-18.
- [21] Theoharides TC. Neuroendocrinology of mast cells: Challenges
and controversies. Exp Dermatol 2017; 26(9): 751-759.
[22] Koyuncu Irmak D, Kilinc E, Tore F. Shared fate of meningeal
mast cells and sensory neurons in migraine. Front Cell Neurosci
2019; 13(136): 1-10.
- [23] Kilinc E, Tore F, Dagistan Y, Bugdayci G. Thymoquinone inhibits
neurogenic inflammation underlying migraine through
modulation of calcitonin gene-related peptide release and
stabilization of meningeal mast cells in glyceryltrinitrate-
induced migraine model in rats. Inflammation 2020; 43(1):264-273.