1 Table S1. List of proteins identified by mass spectrometry within the resolving (24 h) 2 pleural exudate. MW Number of Total Peptide Spectra No. Identified Proteins UniProt ID (kDa) #123 #4 #5 #6 #7 #8 #9 Total 1 Alpha-1-acid glycoprotein A1AG 24 0 2 1 0 0 3 3 9 2 Alpha-1-antiproteinasea AAT 52 23 11 37 12 10 31 20 144 3 Alpha-1-inhibitor 3 A1I3 164 72 3 0 8 113 52 27 275 4 Alpha-1-macroglobulin A1M 167 15 0 0 0 95 19 15 144 5 Alpha-2-macroglobulin A2MG 164 3 0 0 0 14 0 0 17 6 Actin, cytoplasmic 1 ACTB 42 0 5 0 0 0 1.5 0 7 7 Afamin AFAM 69 0 53 3 13 21 11 13 114 8 Serum albumin ALBU 69 52 143 235 179 105 233 215 1161 9 Protein AMBP AMBP 39 0 1 0 2 0 4 0 7 10 Angiotensinogen ANGT 52 0 0 4 0 0 4 0 8 11 Apolipoprotein A-I APOA1 30 7 0 0 0 23 3 0 33 12 Apolipoprotein A-IV APOA4 44 0 0 8 0 11 4 0 23 13 Apolipoprotein E APOE 36 5 0 0 0 10 0 0 15 14 Beta-2-glycoprotein 1 APOH 33 0 11 2 2 0 4 4 23 15 Attractin ATRN 159 5 0 0 0 5 0 0 10 16 Cathepsin B CATB 37 0 0 4 0 0 2 0 6 17 Corticosteroid-binding globulin CBG 45 0 11 0 0 0 2 0 13 18 Carboxypeptidase B2 CBPB2 49 0 0 2 0 0 2 0 4 19 Carboxypeptidase Q CBPQ 52 0 6 0 0 0 0 0 6 20 Ceruloplasmin CERU 121 0 49 2 8 12 17 9 97 21 Complement factor I CFAI 67 0 14 0 0 2 3 1 20 22 Clusterin CLUS 51 0 0 0 0 4 0 0 4 23 Complement C3 CO3 186 3 45 3 30 63 37 13 194 24 Complement C4 CO4 192 5 0 0 4 16 4 2 31 25 Complement component C9 CO9 62 0 6 0 0 0 0 0 6 26 C-reactive protein CRP 25 0 0 0 3 8 0 0 11 27 Carboxylesterase 1C EST1C 60 0 18 12 9 2 7 8 56 28 Alpha-2-HS-glycoprotein FETUA 38 0 16 17 0 4 14 7 58 29 Fetuin-B FETUB 42 0 0 15 0 0 16 0 31 30 Fibrinogen alpha chain FIBA 87 4 5 2 0 17 2 2 32 31 Fibrinogen beta chain FIB 54 4 2 0 0 16 0 1 23 32 Fibrinogen gamma chain FIB 51 8 4 0 0 19 4 2 37 33 Gelsolin GLS 80 0 9 7 0 2 9 0 27 34 Hemoglobin subunit alpha-1/2 HB 15 0 0 0 0 6 2 0 8 35 Hemoglobin subunit beta-1 HBB1 16 0 0 0 2 5.5 0 0 7 36 Hemopexin HX 60 2 65 39 8.5 21 43 24 202 37 Haptoglobin HPT 39 6 13 0 13 24 12 10 78 38 Histidine-rich glycoprotein HRG 59 6 0 0 5 12 0 2 25 39 Plasma protease C1 inhibitor IC1 56 0 0 0 0 5 0 0 5 40 Ig gamma-2A chain C region IGG2A 35 0 4 0 3 7 2 0 16 41 Ig gamma-2B chain C region IGG2B 36 0 2 0 2 0 0 0 4 42 Ig gamma-2C chain C region IGG2C 37 0 4 0 4 5 5 0 18 43 Ig gamma-1 chain C region IGHG1 36 0 0 0 0 2 0 0 2 44 Inter-alpha-trypsin inhibitor heavy chain H3 ITIH3 99 0 0 0 0 8 2 0 10 45 Ig kappa chain C region, B allele KACB 12 0 11 0 5 16 8 4 44 46 Kininogen-1 KNG1 71 0 0 0 0 2 0 0 2 47 T-kininogen 1 KNT1 48 0 5 0 0 0 0 0 5 48 T-kininogen 2 KNT2 48 0 35 10 4 7 8 12 76 49 Ig lambda-2 chain C region LAC2 11 0 0 0 0 3 0 0 3 50 Murinoglobulin-1 MUG1 165 16 0 0 0 31 13 3 63 51 Phosphatidylinositol-glycan- specific phospholipase D PHLD 94 0 0 0 0 2 0 0 2 52 Plasminogen PLMN 91 0 23 27 0 7 24 4 85 53 Serine protease inhibitor A3K SPA3K 47 0 19 4 0 0 8 5 36 54 Serine protease inhibitor A3L SPA3L 46 2 32 22 10 4 23 7 100 55 Serine protease inhibitor A3M (Fragment) SPA3M 46 0 7 2 0 0 2 0 11 56 Serine protease inhibitor A3N SPA3N 47 0 17 20 4 0 19 5 65 57 Prothrombin THRB 70 0 19 2 0 1.5 10 0 33 58 Serotransferrin TRFE 76 3 86 79 20 35 68 75 366 59 Transthyretin TTHY 16 0 0 7 0 4 7 3 21 60 Vitamin D-binding protein VTDB 54 0 22 29 9 10 22 12 104 61 Zinc-alpha-2-glycoprotein ZA2G 34 0 0 0 0 0 1 0 1 3 Analysis was conducted on a pool of six separate exudate samples, in duplicate. 4 a In bold we indicate the proteins further investigated in this study. 1 Table S2. Effect of selected proteins on cytokine secretion in the presence of IL-1β. IL-6 IL-8 Treatment (pg/ml) (pg/ml) IL-1β + Vehicle 4313 ± 86 3130 ± 133 IL-1 + AAT (µg/ml) β 2539 ± 41 ** 3 3670 ±110 10 3402 ± 55 2748 ± 54 * 30 2790 ± 223 ** 3157 ± 88 IL-1 + GSN (µg/ml) β 3227 ± 95 0.1 3280 ± 74 * 0.3 3666.8 ± 222.9 4079 ±116 ** 1 3537.2 ± 81.2 3440 ± 71 IL-1β + Hx (µg/ml) 3 185 ± 34 *** 2146 ± 25 *** 10 422 ±112 *** 3305 ± 177 30 495 ± 13 *** 3542 ± 154

2 Human C-28/I2 chondrocyte micromasses were incubated with IL-1β (20 ng/ml) for 48h in the presence of the 3 indicated proteins, or vehicle, and cytokine levels measured in cell-free supernatants. Data are Mean±SEM of 4 three experiments performed in triplicate. *p<0.05, **p<0.01, ***p<0.0001 compared to IL-1β (One-Way ANOVA 5 followed by Dunnet’s post-test). 6