Inflammatory and Immunological Responses to Hyaluronan Preparations

Ottaviani, Robert A.; Wooley, Paul H.; Song, Zheng; Markel, David C.

doi:10.2106/00004623-200701000-00020

Cited by 17 publications

(27 citation statements)

References 19 publications

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“…Widely distributed hyaluronan products, such as Synvisc, Hyalgan and Supartz were investigated by BALB/c mice. These results demonstrated that all three hyaluronan products can cause an inflammatory soft‐tissue reaction . The adverse reactions relate to three main causes: impurities, concentration, and excessive amount of product injected, and injection technique .…”

Section: Discussionmentioning

confidence: 79%

“…These results demonstrated that all three hyaluronan products can cause an inflammatory soft-tissue reaction. 39 The adverse reactions relate to three main causes: impurities, concentration, and excessive amount of product injected, and injection technique. 1,2,[39][40][41] The three main causes of the inflammatory reactions require additional research that finally will lead to improvement of treatments with these products.…”

Section: Discussionmentioning

confidence: 99%

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Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β production

Baeva

Lyle

Rios

et al. 2013

J Biomedical Materials Res

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This study examined the effect of hyaluronan (HA) molecular weight on immune response. HA with molecular weights ranging from the unitary disaccharide unit (400 Da) up to 1.7 × 10(6) Da and with very low endotoxin contamination level (less than 0.03 EU/mg) was used. Primary human monocyte/macrophage cultures were assayed for IL-1β production under a variety of inflammatory conditions with or without HA. Under the highest inflammatory states, production of interleukin 1β (IL-1β) was suppressed in the presence of high molecular weight hyaluronan (HMW-HA) and in the presence of low molecular weight hyaluronan (LMW-HA) at mg/mL concentrations. There was variability in the sensitivity of the response to HA fragments with MW below 5000 Da at micromolar concentrations. There was variability in IL-1β cytokine productions from donor to donor in unstimulated human cell cultures. This study supplements our previous published study that investigated the immunogenic effect of HA molecular weights using murine cell line RAW264.6, rat splenocytes, and rat adherent differentiated primary macrophages. These data support the hypothesis that if the amount of endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke normal tissue macrophage-mediated inflammatory reactions.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β production

Baeva

Lyle

Rios

et al. 2013

J Biomedical Materials Res

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“…The study followed established experimental techniques that were used previously to examine the biocompatibility of viscosupplements in mice. 15 To examine immune specificity in response to viscosupplements, 54 mice were prebled before experimentation, and sera was separated and stored at À80 C. Air pouches were established in 30 Balb/c mice as described previously. Mice were anesthetized, and the dorsal area was shaved and injected subcutaneously with 2.5 mL air for every 48 h to establish the air pouch.…”

Section: Animals and Immunization Techniquesmentioning

confidence: 99%

Hyaluronic acid viscosupplements from avian and non‐mammalian sources exhibit biocompatibility profiles with unique, source‐specific, antigenic profiles

Wooley¹,

Zheng²,

Harrison³

2012

J Biomed Mater Res

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The objective of this study was to evaluate and compare the biocompatibility profiles of hyaluronic acid (HA) viscosupplements from avian and non-mammalian sources. Inflammatory and immune reactions were assessed in models of both clinically relevant and stringent immunological exposure conditions. Experiments were conducted to evaluate tissue reactions and immunological responses and assess antibody formation with the capacity to bind directly to and cross-react with the different viscosupplements. Mice were exposed to viscosupplements using the air pouch inflammation model and specific immunization using Freund's complete adjuvant (FCA). Murine pouch membrane tissue reactions revealed generally mild to moderate responses, with cellular infiltration and cytokine profiles of pouch tissue characteristic of predominantly fibroblastic responses rather than marked inflammatory reactions. In vitro testing indicated that pouch injections did not elicit detectable T-cell proliferative responses, while antibody assays revealed that mice immunized with viscosupplements in FCA and subsequently boosted were capable of mounting an antibody response with a range of specificities. High reactivity to avian serum albumin was seen in sera from mice injected with HA from an avian source, while low positive reactivity to the bacterial antigen Staphylococcal Lipotechoic Acid was observed in sera from mice injected with HA from bacterial sources. These specificities did not indicate any propensity to cross-react, suggesting that patients with adverse immune responses to HA from an avian source should be unresponsive to subsequent injection with HA from a non-avian source. Overall, the findings demonstrate that viscosupplements exhibit good biocompatibility profiles in the murine air pouch, but when provoked to elicit immunological reactions exhibit unique antigenic spectra. These findings suggest that an immunologically mediated immune reaction directed against avian proteins should not necessarily be a contraindication for the administration of non-avian viscosupplements.

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“…The likelihood of these reactions increases up to 8-fold in those who pursue multiple treatment sessions [12]. Studies have found a varying antibody response to different sources of hyaluronan with Synvisc (Sanofi-Aventis, Bridgewater, NJ) eliciting the greatest immunogenic response in limited animal models [13], [14]. However, other products have also been described to cause similar reactions of varying severity [10].…”

Section: Introductionmentioning

confidence: 99%

Late hemorrhagic pseudoseptic arthritis encountered during total knee arthroplasty due to hyaluronic acid viscosupplementation

2016

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Osteoarthritis (OA) is the most common form of arthritis and affects approximately one-third of people in the United Sates aged 65 years and older. Since 2013, the American Academy of Orthopaedic Surgeons has not been able to recommended using hyaluronic acid for patients with symptomatic OA of the knee. Subsequent publications have also cautioned against the use of viscosupplementation based on lack of efficacy and the potential for harm. We present a case of late hemorrhagic pseudoseptic arthritis encountered during TKA due to hyaluronic acid viscosupplementation. Our triad of findings includes (1) acute and chronic inflammatory cells on frozen section, (2) synovitis with hemosiderin deposition, and (3) blackened cartilage with iron deposition on permanent histopathology. Our case is unique in that it shows a previously undescribed late complication of viscosupplementation.

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Inflammatory and Immunological Responses to Hyaluronan Preparations

Cited by 17 publications

References 19 publications

Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β production

Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β production

Hyaluronic acid viscosupplements from avian and non‐mammalian sources exhibit biocompatibility profiles with unique, source‐specific, antigenic profiles

Late hemorrhagic pseudoseptic arthritis encountered during total knee arthroplasty due to hyaluronic acid viscosupplementation

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