Limits...
Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

Van der Watt JJ, Wilkinson KA, Wilkinson RJ, Heckmann JM - BMC Infect. Dis. (2014)

Bottom Line: The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12.The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels.Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neurology, Department of Medicine, University of Cape Town, Observatory, Cape Town 7925, South Africa. jjvanderwatt@gmail.com.

ABSTRACT

Background: In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study.

Methods: One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays.

Results: Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002).

Conclusions: The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

Show MeSH

Related in: MedlinePlus

Longitudinal evaluation of candidate pro-inflammatory/anti-inflammatory cytokine and cytokine/receptor ratios categorized by incident neuropathic symptom status. Incident neuropathic symptoms developed within 12 weeks of starting cART. The control group refers to the symptom-free nested control group paired for previously identified risk factors. *refers to within-group differences from baseline, p < 0.05. # refers to between-group differences from baseline levels, p < 0.05. Horizontal bars indicate median values with interquartile ranges. Baseline refers to pre-cART levels. Abbreviations: IL, interleukin; sIL, soluble interleukin; TNFα, tumour necrosis factor-α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928502&req=5

Figure 2: Longitudinal evaluation of candidate pro-inflammatory/anti-inflammatory cytokine and cytokine/receptor ratios categorized by incident neuropathic symptom status. Incident neuropathic symptoms developed within 12 weeks of starting cART. The control group refers to the symptom-free nested control group paired for previously identified risk factors. *refers to within-group differences from baseline, p < 0.05. # refers to between-group differences from baseline levels, p < 0.05. Horizontal bars indicate median values with interquartile ranges. Baseline refers to pre-cART levels. Abbreviations: IL, interleukin; sIL, soluble interleukin; TNFα, tumour necrosis factor-α.

Mentions: The balance of pro- and anti-inflammatory cytokines may be as important as individual cytokine concentrations. Therefore, we assessed ratios of pro- and anti-inflammatory cytokines and their soluble receptors as markers of a dysregulated immune response [29-32]. At week 2, the symptomatic group compared with the control group showed lower ratios of cytokines to soluble cytokine receptors: IL-1β/sIL-1RI (p = 0.004), IL-1β/IL-1RA (p = 0.006) and IL-2/sIL-2Rα (p = 0.014) (Figure 2). At the same time point, the “pain-associated” cytokines of a priori interest showed higher ratios in the symptomatic group for TNFα/IL-4 (p = 0.022) and a trend for IL-6/IL-4 (p = 0.054) and IFNγ/IL-4 (p = 0.061). At week 12 the symptomatic group still had a higher IFNγ/IL-10 ratio (p = 0.044) (Figure 2).


Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

Van der Watt JJ, Wilkinson KA, Wilkinson RJ, Heckmann JM - BMC Infect. Dis. (2014)

Longitudinal evaluation of candidate pro-inflammatory/anti-inflammatory cytokine and cytokine/receptor ratios categorized by incident neuropathic symptom status. Incident neuropathic symptoms developed within 12 weeks of starting cART. The control group refers to the symptom-free nested control group paired for previously identified risk factors. *refers to within-group differences from baseline, p < 0.05. # refers to between-group differences from baseline levels, p < 0.05. Horizontal bars indicate median values with interquartile ranges. Baseline refers to pre-cART levels. Abbreviations: IL, interleukin; sIL, soluble interleukin; TNFα, tumour necrosis factor-α.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928502&req=5

Figure 2: Longitudinal evaluation of candidate pro-inflammatory/anti-inflammatory cytokine and cytokine/receptor ratios categorized by incident neuropathic symptom status. Incident neuropathic symptoms developed within 12 weeks of starting cART. The control group refers to the symptom-free nested control group paired for previously identified risk factors. *refers to within-group differences from baseline, p < 0.05. # refers to between-group differences from baseline levels, p < 0.05. Horizontal bars indicate median values with interquartile ranges. Baseline refers to pre-cART levels. Abbreviations: IL, interleukin; sIL, soluble interleukin; TNFα, tumour necrosis factor-α.
Mentions: The balance of pro- and anti-inflammatory cytokines may be as important as individual cytokine concentrations. Therefore, we assessed ratios of pro- and anti-inflammatory cytokines and their soluble receptors as markers of a dysregulated immune response [29-32]. At week 2, the symptomatic group compared with the control group showed lower ratios of cytokines to soluble cytokine receptors: IL-1β/sIL-1RI (p = 0.004), IL-1β/IL-1RA (p = 0.006) and IL-2/sIL-2Rα (p = 0.014) (Figure 2). At the same time point, the “pain-associated” cytokines of a priori interest showed higher ratios in the symptomatic group for TNFα/IL-4 (p = 0.022) and a trend for IL-6/IL-4 (p = 0.054) and IFNγ/IL-4 (p = 0.061). At week 12 the symptomatic group still had a higher IFNγ/IL-10 ratio (p = 0.044) (Figure 2).

Bottom Line: The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12.The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels.Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neurology, Department of Medicine, University of Cape Town, Observatory, Cape Town 7925, South Africa. jjvanderwatt@gmail.com.

ABSTRACT

Background: In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study.

Methods: One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays.

Results: Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002).

Conclusions: The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

Show MeSH
Related in: MedlinePlus